Article Data

  • Views 513
  • Dowloads 109

Original Research

Open Access

Breast cancer - new aspects of tumor biology: are calcitriol and cyclooxygenase-2 possible targets for breast cancer?

  • M. Thill1
  • A. Terjung2
  • M. Friedrich2,*,

1Department of Obstetrics and Gynecology, University Schleswig-Holstein, Campus Luebeck, Luebeck

2Department of Gynecology and Obstetrics, Helios Hospital Krefeld, Krefeld (Germany)

DOI: 10.12892/ejgo26182014 Vol.35,Issue 4,July 2014 pp.341-358

Published: 10 July 2014

*Corresponding Author(s): M. Friedrich E-mail:


Up until now there have been many advances in treatment options for breast cancers such as targeted therapies like monoclonal antibodies, tyrosine kinase inhibitors, mTOR antagonists, and vaccines. Despite these advances, there are still many more that warrant further exploration. Two of these targets might be the cyclooxygenase-2 (COX-2), the key enzyme required to convert arachidonic acid to prostaglandins, and calcitriol [1,25(OH)2D3]which is the biologically active form of vitamin D. Both calcitriol and the inhibition of COX-2 have shown antiproliferative and prodifferentiation, as well as pro-apoptotic effects in different malignancies in vitro and in vivo, and the key prostaglandin catabolic enzyme 15-hydroxyprostaglandin dehydrogenase (15-PGDH) is known to have tumor suppressor activity. Furthermore, the combination of calcitriol and nonsteroidal anti-inflammatory drugs (NSAIDs), such as non-selective and selective COX-2 inhibitors, acting synergistically to achieve significant cell growth inhibition in prostate cancer. Some epidemiological studies suggest that vitamin D confers a moderate benefit against breast cancer while most epidemiological studies presume that NSAIDs confer the same. Nevertheless there is growing body of evidence that COX-2 expression is a fundamental step in breast cancer carcinogenesis. To date, clinical trials have been conducted in patients with different malignancies using treatment strategies including COX-2 inhibitors and calcitriol and are showing partially encouraging results. The goal of this review is to shed light on the association between the prostaglandin as well as vitamin D metabolism relating to the incidence and therapy of breast cancers. Moreover, this review will also highlight potential treatment options, as well as extract any existing interactions between the two metabolisms.


Prostaglandin; Vitamin D; Calcitriol; Cyclooxygenase-2 (COX-2); Breast cancer.

Cite and Share

M. Thill,A. Terjung,M. Friedrich. Breast cancer - new aspects of tumor biology: are calcitriol and cyclooxygenase-2 possible targets for breast cancer?. European Journal of Gynaecological Oncology. 2014. 35(4);341-358.


[1] American Cancer Society: “Cancer facts and figures 2005”. Atlanta: American Cancer Society, 2005, 9. Available at:

[2] Ozols R. F., Rubins S. C., Dembo A. J., Robboy, S.: “Gynecologic oncology: epithelial ovarian cancer”. Hoskins W. J., Perez C. A., Young R. C.(eds). Philadelphia: Lippincott Williams & Wilkins, 1992, 731.

[3] FIGO (International Federation of Gynecology and Obstetrics): “Annual report on the results of treatment in gynecological cancer”. Int. J. Gynaecol. Obstet., 2003, 83, 1.

[4] Ferrandina G., Lauriola L., Zannoni G. F., Fagotti A., Fanfani F., Legge F., et al.: “Increased cyclooxygenase-2 (COX-2) expression is associated with chemotherapy resistance and outcome in ovarian cancer patients. Ann. Oncol. 2002, 13, 1205.

[5] Singh-Ranger G.; Salhab M.; Mokbel K.: “The role of cyclooxygenase-2 in breast cancer: review”. Breast Cancer Res. Treat., 2008, 109, 189.

[6] Coussens L.M.; Werb Z.: “Inflammation and cancer”. Nature, 2002, 420, 860.

[7] Park E.A.: “The etiology of rickets”. Physiol. Rev., 1923, 3, 106.

[8] Deluca H. F., Cantorna M. T.: “Vitamin D: its role and uses in immunology”. FASEB J., 2001, 15, 2579.

[9] Guyton K. Z., Kensler T. W., Posner G. H.: “Vitamin D and vitamin D analogs as cancer chemopreventive agents”. Nutr. Rev., 2003, 61, 227.

[10] Jones G., Strugnell S. A., Deluca H. F.: “Current understanding of the molecular actions of vitamin D”. Physiol. Rev., 1998, 78, 1193.

[11] Adorini L.: “Immunomodulatory effects of vitamin D receptor ligands in autoimmune diseases”. Int. Immunopharmacol., 2002, 2, 1017–1028.

[12] Colston, K. W.; Hansen, C. M. Mechanisms implicated in the growth regulatory effects of vitamin D in breast cancer. Endocr. Relat. Cancer, 2002, 9, 45.

[13] Johnson C. S., Hershberger P. A., Trump D. L.: “Vitamin D-related therapies in prostate cancer.” Cancer Metastasis Rev., 2002, 21, 147.

[14] Mathieu C., Adorini L.: “The coming of age of 1,25-dihydroxyvitamin D3 analogs as immunomodulatory agents”. Trends Mol. Med., 2002, 8, 174.

[15] O’Kelly J., Koeffler H.P.: “Vitamin D analogs and breast cancer”. Recent Results Cancer Res., 2003, 164, 333.

[16] van den Bemd G. J., Chang G.T.: “Vitamin D and vitamin D analogs in cancer treatment”. Curr. Drug Targets, 2002, 3, 85.

[17] Welsh J., Wietzke J.A., Zinser G.M., Byrne B., Smith K., Narvaez C.J.: “Vitamin D3 receptor as a target for breast cancer prevention”. J. Nutr., 2003, 133, 2425.

[18] Garland C.F., Garland F.C., Gorham E.D.: “Calcium and vitamin D. Their potential roles in colon and breast cancer prevention”. Ann. N. Y. Acad. Sci., 1999, 889, 107.

[19] Janowsky E.C., Lester G.E., Weinberg C.R., Millikan R.C., Schildkraut J.M., Garrett P. A., Hulka B.S.: “Association between low levels of 1,25-dihydroxyvitamin D and breast cancer risk”. Public Health Nutr., 1999, 2, 283.

[20] Shin M.H., Holmes M.D., Hankinson S.E., Wu K., Colditz G.A., Willett W.C.: “Intake of dairy products, calcium, and vitamin D and risk of breast cancer”. J. Natl. Cancer Inst., 2002, 94, 1301.

[21] Studzinski G.P., Moore D.C.: “Sunlight—can it prevent as well as cause cancer?” Cancer Res., 1995, 55, 4014.

[22] Gorham E.D., Garland F.C., Garland C.F.: “Sunlight and breast cancer incidence in the USSR”. Int. J. Epidemiol., 1990, 19, 820.

[23] Garland F.C., Garland C.F., Gorham E.D., Young J.F.: “Geographic variation in breast cancer mortality in the United States: a hypothesis involving exposure to solar radiation”. Prev. Med., 1990, 19, 614.

[24] Blot W.J., Fraumeni J.F. Jr., Stone B.J.: “Geographic patterns of breast cancer in the United States”. J. Natl. Cancer. Inst., 1977, 59, 1407.

[25] Malloy P.J., Pike J.W., Feldman D.: “The vitamin D receptor and the syndrome of hereditary 1,25-dihydroxyvitamin D-resistant rickets”. Endocr. Rev., 1999, 20, 156.

[26] Liu, M., Lee M.H. Cohen M., Bommakanti M., Freedman L.P.: “Transcriptional activation of the Cdk inhibitor p21 by vitamin D3 leads to the in-duced differentiation of the myelomonocytic cell line U937”. Genes Dev., 1996, 10, 142.

[27] Polly P., Carlberg C., Eisman J. A., Morrison N.A.: “Identification of a vitamin D3 response element in the fibronectin gene that is bound by a vi-tamin D3 receptor homodimer”. J. Cell. Biochem., 1996, 60, 322.

[28] Polly P., Carlberg C., Eisman J.A., Morrison N.A.: “1a,25-dihydroxyvitamin D3 receptor as a mediator of transrepression of retinoid signaling”. J. Cell. Biochem., 1997, 67, 287.

[29] Berger U., Wilson P., McClelland R.A., Colston K., Haussler M.R., Pike J.W., Coombes R.C.: “Immunocytochemical detection of 1,25-dihydrox-yvitamin D receptors in normal human tissues”. J. Clin. Endocrinol. Metab., 1988, 67, 607.

[30] Stack E., DuBois R.N.: “Regulation of cyclo-oxygenase-2”. Best Pract. Res. Clin. Gastroenterol., 2001, 15, 787.

[31] Murakami M., Kudo I.: “Recent advances in molecular biology and physiology of the prostaglandin E2-biosynthetic pathway”. Prog. Lipid. Res., 2004, 43, 3.

[32] Anggard E.: “The biological activities of three metabolites of prostaglandin E1”. Acta Physiol. Scand., 1966, 66, 509.

[33] Tsuboi K., Sugimoto Y., Ichikawa A.: “Prostanoid receptor subtypes”. Prostaglandins Other Lipid. Mediat., 2002, 68, 535.

[34] Williams C.S., DuBois R.N.: “Prostaglandin endoperoxide synthase: why two isoforms?” Am. J. Physiol., 1996, 270, 393.

[35] Herschman H.R.: “Prostaglandin synthase 2”. Biochim. Biophys. Acta., 1996, 1299, 125.

[36] Langenbach R., Morham S.G., Tiano, H.F., Loftin C.D., Ghanayem B.I., Chulada P.C., et al.: “Prostaglandin synthase 1 gene disruption in mice reduces arachidonic acid-induced inflammation and indomethacin-induced gastric ulceration”. Cell, 1995, 83, 483.

[37] Lim H., Paria B.C., Das S.K., Dinchuk J.E., Langenbach R., Trzaskos J.M., Dey S.K.: “Multiple female reproductive failures in cyclooxygenase 2- deficient mice”. Cell, 1997, 91, 197.

[38] Davis B.J., Lennard D.E., Lee C.A., Tiano H.F., Morham S.G., Wetsel W.C., Langenbach R.: “Anovulation in cyclooxygenase-2 deficient mice is restored by prostaglandin E2 and interleukin-1 beta”. Endocrinology, 1999, 140, 2685.

[39] Loftin C.D., Trivedi, D.R., Tiano H.F., Clark JA., Lee C. A., Epstein, J. A., et al.: “Failure of ductus arteriosus closure and remodelling in neona-tal mice deficient in cyclooxygenase-1 and -2”. Proc. Natl. Acad. Sci. U.S.A., 2001, 98, 1059.

[40] Rozic J.G., Chakraborty C., Lala P.K.: “Cyclooxygenase inhibitors retard murine mammary tumor progression by reducing tumor cell migration, invasiveness and angiogenesis”. Int. J. Cancer, 2001, 93, 497.

[41] Eberhart C.E., Coffey R.J., Radhika A., Giardiello F.M.: Ferrebach S., Dubois R.N.: “Up-regulation of cyclooxygenase gene expression in human colorectal adenomas and adenocarcinomas”. Gastroenterology, 1994, 107, 1183.

[42] Sinicrope F. A., Lemoine M., Xi L., Lynch P.M., Cleary K.R., Shen Y., Frazier, M.L.: “Reduced expression of cyclooxygenase 2 proteins in hereditary nonpolyposis colorectal cancers relative to sporadic cancers”. Gastroenterology, 1999, 117, 350.

[43] Ristimaki A., Honkanen N., Jankala H., Sipponen P., Harkonen M.: “Expression of cyclooxygenase-2 in human gastric carcinoma”. Cancer Res., 1997, 57, 1276.

[44] Zimmermann K.C., Sarbia M., Weber A., Bochard F., Gabbert H.E., Schror K.: “Cyclooxygenase-2 expression in human esophageal carcinoma”. Cancer Res., 1999, 5, 198.

[45] Swami S., Krishnan A.V., Moreno J., Bhattacharyya R.B., Peehl D., Feldman D.: “Calcitriol and enistein actions to inhibit the prostaglandin pathway: potential combination therapy to treat prostate cancer.” J. Nutr., 2007, 137, 205S.

[46] Subbaramaiah K., Dannenberg A.J.: “Cyclooxygenase 2: a molecular target for cancer prevention and treatment”. Trends Pharmacol. Sci., 2003, 24, 96.

[47] Heinonen P.K., Metsa-Ketela T.: “Prostaglandin and thromboxane production in ovarian cancer tissue”. Gynecol. Obstet. Invest., 1984, 18, 225.

[48] Ylikorkala O., Kauppila A., Viinikka L.: “Prostacyclin and thromboxane in ovarian cancer: effect of cytostatics and prostaglandin synthesis inhibitors”. Gynecol. Oncol., 1983, 16, 340.

[49] Munkarah A.R., Morris R., Baumann P., Deppe G., Malone J., Diamond M.P., Saed G.M.: “Effects of prostaglandin E(2) on proliferation and apoptosis of epithelial ovarian cancer cells”. J. Soc. Gynecol. Investig., 2002, 9, 168.

[50] Gupta R.A., Tejada L.V., Tong B.J., Das S.K., Morrow J.D., Dey S.K., DuBois R.N.: “Cyclooxygenase-1 is overexpressed and promotes angiogenic growth factor production in ovarian cancer”. Cancer Res., 2003, 63, 906.

[51] Ali-Fehmi R., Morris R.T., Bandyopadhyay S., Che M., Schimp V., Malone J.M. Jr., Munkarah A.R.: “Expression of cyclooxygenase-2 in advanced stage ovarian serous carcinoma: correlation with tumor cell proliferation, apoptosis, angiogenesis, and survival”. Am. J. Obstet. Gynecol., 2005, 192, 819.

[52] Daikoku T., Wang D., Tranguch S., Morrow J.D., Orsulic S., DuBois R.N., Dey S.K.: “Cyclooxygenase-1 is a potential target for prevention and treatment of ovarian epithelial cancer”. Cancer Res., 2005, 65, 3735.

[53] Dore M., Cote L.C., Mitchell A., Sirois J.: “Expression of prostaglandin G/H synthase type 1, but not type 2, in human ovarian adenocarcinomas”. J. Histochem. Cytochem., 1998, 46, 77.

[54] Daikoku T., Tranguch S., Trofimova I.N., Dinulescu D.M., Jacks T., Nikitin A.Y., et al.: “Cyclooxygenase-1 is overexpressed in multiple genetically engineered mouse models of epithelial ovarian cancer”. Cancer Res., 2006, 66, 2527.

[55] Rodriguez-Burford C., Barnes M.N., Oelschlager D.K., Myers R.B., Talley L.I., Partridge E.E., Grizzle W.E.: “Effects of nonsteroidal anti-inflammatory agents (NSAIDs) on ovarian carcinoma cell lines: preclinical evaluation of NSAIDs as chemopreventive agents”. Clin. Cancer Res., 2002, 8, 202.

[56] Schreinemachers D.M., Everson R.B.: “Aspirin use and lung, colon, and breast cancer. Incidence in a prospective study”. Epidemiology, 1994, 5,138.

[57] Harris, R.E., Namboodiri K.K., Farrar W.B.: “Non-steroidal anti-inflammatory drugs and breast cancer”. Epidemiology, 1996, 7, 203.

[58] Sharp C.R., Collet J.P., McNutt M., Belzile E., Boivin J.F., Hanley J. A.: “Nested case control study of the effect of non-steroidal anti-inflammatory drugs on breast cancer risk and stage”. Br. J. Cancer, 2000, 83, 112.

[59] Liu, X., Rose, D. Differential expression and regulation of cyclooxygenase-1 and -2 in two human breast cancer cell lines. Cancer Res. 1996, 56, 5125.

[60] Schrey, M. P., Patel, K. V. Prostaglandin E2 production and metabolism in human breast cancer cells and breast fibroblasts. Regulation by inflammatory mediators. Br. J. Cancer, 1995, 72, 1412.

[61] Rolland P.H., Martin P.M., Jacquemier J., Rolland, A., Toga M.: “Prostaglandins in human breast cancer: evidence suggesting that elevated prostaglandin production is a marker of high metastatic potential for neoplastic cells”. J. Natl. Cancer Inst. (Bethesda), 1980, 64, 1061.

[62] Karmali R.A., Welts S., Thaler H.T., Lefevre F.: “Prostaglandins in breast cancer. Relationship to disease stage and hormone status”. Br. J. Cancer, 1983, 48, 689-696.

[63] Kawamori T., Wakabayashi K.: “COX-2 and prostanoid receptors: good targets for chemoprevention”. J. Environ. Pathol. Toxicol. Oncol., 2002, 21, 149.

[64] Sonoshita M., Takaku K., Sasaki N., Sugimoto Y., Ushikubi F., Narumiya S., et al.: “M. Acceleration of intestinal polyposis through prostaglandin receptor EP2 in Apc(Delta 716) knockout mice”. Nat. Med., 2001, 7, 1048.

[65] Zha S., Yegnasubramanian V., Nelson W.G., Isaacs W. B., De Marzo,A.M.: “Cyclooxygenases in cancer: progress and perspective”. Cancer Lett., 2004, 215.

[66] Chang S.H., Liu C.H., Conway R., Han D.K., Nithipatikom K., Trifan O.C., et al.: “Role of prostaglandin E2-dependent angiogenic switch in cyclooxygenase 2-induced breast cancer progression”. Proc. Natl. Acad. Sci. USA, 2004, 101, 591.

[67] Yan M., Rerko, R.M., Platzer P., Dawson D., Willis J., Tong M., et al.: “15-Hydroxyprostaglandin dehydrogenase, a COX-2 oncogene antagonist, is a TGF-beta-induced suppressor of human gastrointestinal cancers”. Proc. Natl. Acad. Sci. USA, 2004, 101, 17468.

[68] Ding Y., Tong M., Liu S., Moscow J.A., Tai H.H.: “NAD+-linked 15-hydroxyprostaglandin dehydrogenase (15-PGDH) behaves as a tumor suppressor in lung cancer”. Carcinogenesis 2005, 26, 65.

[69] Gee J.R., Montoya R.G., Khaled H.M., Sabichi A.L., Grossman H.B.: “Cytokeratin 20, AN43, PGDH, and COX-2 expression in transitional and squamous cell carcinoma of the bladder”. Urol. Oncol., 2003, 21, 266.

[70] Wolf I., O’Kelly J., Rubinek T., Tong M., Nguyen A., Lin B.T., et al.: “15-hydroxyprostaglandin dehydrogenase is a tumor suppressor of human breast cancer”. Cancer Res., 2006, 66, 7818.

[71] van ‘t Veer L.J., Dai H., van de Vijver M.J., He Y.D., Hart A.A., Mao M., et al.: “Gene expression profiling predicts clinical outcome of breast cancer”. Nature, 2002, 415, 530.

[72] Half E., Tang X.M., Gwyn K., Sahin A., Wathen K., Sinicrope F. A.: “Cyclooxygenase-2 expression in human breast cancers and adjacent ductal carcinoma in situ”. Cancer Res., 2002, 62, 1676.

[73] Denkert C., Winzer K.J., Müller B.M., Weichert W., Pest S., Köbel M., et al.: “Elevated expression of cyclooxygenase-2 is a negative prognostic factor for disease free survival and overall survival in patients with breast carcinoma”. Cancer 2003, 97(12), 2978.

[74] Ristimäki A., Sivula A., Lundin J., Lundin M., Salminen T., Haglund C., et al.: “Prognostic significance of elevated cyclooxygenase-2 expression in breast cancer”. Cancer Res., 2002, 62, 632.

[75] Singh Ranger G., Thomas V., Jewell A., Mokbel K.: “Elevated cyclooxygenase-2 expression correlates with distant metastases in breast cancer”. Anticancer Res., 2004, 24, 2349.

[76] Nassar A., Radhakishnan A., Cabero I.A., Cotsonis G., Cohen C.: “COX-2 expression in invasive breast cancer: Correlation with prognostic parameters and outcome. Appl. Immunohistochem”. Mol. Morphol., 2007, 15, 255.

[77] Hwang D., Scollard D., Byrne J., Levine E.: “Expression of cyclooxygenase-1 and cyclooxygenase-2 in human breast cancer”. J. Natl. Cancer Inst., 1998, 90, 455.

[78] Soslow R., Dannenberg A., Rush D., Woerner B.M., Khan K.N., Masferrer J., Koki A.: “COX-2 is expressed in human pulmonary, colonic, and mammary tumors”. Cancer, 2000, 89, 2637.

[79] Costa C., Soares R., Reis-Filho J.S., Leitão D., Amendoeira I., Schmitt F. C.: “Cyclooxygenase 2 expression is associated with angiogenesis and lymph node metastasis in human breast cancer”. J. Clin. Pathol., 2002, 55, 429.

[80] Kelly L.M., Hill A.D.K., Kennedy S., Connolly E.M., Ramanath R., The S., et al.: “Lack of prognostic effect of COX-2 expression in primary breast cancer on short term follow-up”. Eur. J. Surg. Oncol. 2002, 29, 707.

[81] Lim S.C.: “Role of COX-2, VEGF and cyclin D1 in mammary infiltrating duct carcinoma”. Oncol. Rep., 2003, 10, 1241.

[82] Wülfing P., Diallo R., Müller C., Wülfing C., Poremba C., Heinecke A., et al.: “Analysis of cyclooxygenase-2 expression in human breast cancer: high throughput tissue microarray analysis”. J. Cancer Res. Clin. Oncol., 2003, 129, 375.

[83] Boland G.P., Butt I.P., Prasad R., Knox W.F., Bundred N.J.: “COX-2 expression is associated with an aggressive phenotype in ductal carcinoma in situ”. Br. J. Cancer, 2004, 90, 423.

[84] Zhao X.Q., Pang D., Xue Y.: “Expression of the cyclooxygenase-2 gene in human breast carcinoma”. Zhongua Wai Ke Za Zhi, 2003, 41, 427.

[85] Singh Ranger G., Kirkpatrick K.L., Clark G.M., Mokbel K.: “Cyclooxygenase-2 (COX-2) mRNA expression correlates with progesterone receptor positivity in human breast cancer”. Curr. Med. Res. Opin., 2003, 19, 131.

[86] Kirkpatrick K., Ogunkolade W., Bustin S., Jenkins P., Ghilchik M., Mokbel K.: “The mRNA expression of cyclooxygenase-2 and vascular endothelial growth factor in human breast cancer”. Breast Cancer Res. Treat., 2001, 69, 373.

[87] Watanabe O., Shimizu T., Imamura H., Kinoshita J., Utada Y., Okabe T., et al.: “Expression of cyclooxygenase-2 in malignant and benign breast tumours”. Anticancer Res., 2003, 23, 3215.

[88] Yoshimura N., Sano H., Okamoto M., Akioka K., Ushogome H., Kadotani Y.Y., et al.: “Expression of cyclooxygenase-1 and -2 in human breast cancer”. Surg. Today, 2003, 33, 805.

[89] Ristimäki A., Garfinkel S., Weesendorf J., Maciag T., Hla T.: “Induction of cyclooxygenase-2 by interleukin-1 alpha. Evidence for post-transcriptional regulation”. J. Biol. Chem., 1994, 269, 11769.

[90] Evett G.E., Xie W., Chipman J.G., Robertson D.L., Simmons D.L.: “Prostaglandin GH Synthase isoenyme 2 expression in fibroblasts: regulation by dexamethasone, mitogens and oncogenes”. Arch. Biochem. Biophys., 2003, 306, 169.

[91] Sorlie T., Perou C.M., Tibshirani R.: “Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications”. PNAS USA, 2001, 98, 10869.

[92] Salhab M., Singh-Ranger G., Mokbel R., Jouhra F., Jiang W.G., Mokbel K.: “Cyclooxygenase-2 mRNA expression correlates with aromatase expression in human breast cancer”. J. Surg. Oncol., 2007, 96, 424.

[93] Diaz-Cruz E.S., Shapiro C.L., Brueggemeier R.W.: “Cyclooxygenase inhibitors suppress aromatase expression and activity in breast cancer cells”. J. Clin. Endocrinol. Metab., 2005, 90, 2563.

[94] Richards J.A., Petrel T.A., Brueggemeier RW.: “Signaling pathways regulating aromatase and cyclooxygenases in normal and malignant breast cells”. J. Steroid. Biochem. Mol. Biol., 2002, 80, 203.

[95] Brueggemeier R.W., Richards J.A., Petrel T.A.: “Aromatase and cyclooxygenases: enzymes in breast cancer”. J. Steroid. Biochem. Mol. Biol. 2003, 86, 501.

[96] Vienonen A., Syvala H., Miettinen S., Tuohimaa P., Ylikomi T.: “Expression of progesterone receptor isoforms A and B is differentially regulated by estrogen in different breast cancer cell lines”. J. Steroid. Biochem. Mol. Biol., 2002, 80, 307.

[97] Liu C.H., Chang S., Narko K., Trifan O.C., Wu M., Smith E., et al.: “Overexpression of cyclooxygenase-2 is sufficient to induce tumorigenesis in transgenic mice”. J. Biol. Chem., 2001, 276, 18563.

[98] Tsujii M., DuBois R.N.: “Alterations in cellular adhesion and apoptosis in epithelial cells overexpressing prostaglandin endoperoxide synthase 2”. Cell, 1995, 93, 705.

[99] Oshima M., Dinchuk J.E., Kargman S.L., Oshima H., Hancock B., Kwong E., et al.: “Suppression of intestinal polyposis in Apc716 knockout mice by inhibition of cyclooxygenase-2 (COX-2)”. Cell, 1996, 80, 803.

[100] Mestre J.R., Subbaramaiah K., Sacks P.G., Schantz S.P., Tanabe, T., Inoue H., Dannenberg A.J.: “Retinoids suppress epidermal growth factor-induced transcription of cyclooxygenase-2 in human oral squamous carcinoma cells”. Cancer Res., 1991, 57, 2890.

[101] Davies G., Salter J., Hills M., Martin L.A., Sacks N., Dowsett M.: “Correlation between cyclooxygenase-2 expression and angiogenesis in human breast cancer.” Clin. Cancer Res., 2003, 9, 2651.

[102] Lim S.C., Park S.Y., Do N.Y.: “Correlation of cyclooxygenase-2 pathway and VEGF expression in head and neck squamous cell carcinoma”. Oncol. Rep., 2003, 10, 1073.

[103] Chu J., Lloyd F.L., Trifan O.C., Knapp B., Rizzo M.T.: “Potential involvement of the cyclooxygenase-2 pathway in the regulation of tumor-associated angiogenesis and growth in pancreatic cancer”. Mol. Cancer Ther., 2003, 2, 1.

[104] Tsujii M., Kawano S., Tsujii S., Sawaoka H., Hori M., DuBois N.: “Cyclooxygenase regulates angiogenesis induced by colon cancer cells”. Cell, 1998, 93, 705-716.

[105] Gately, S.: “The contributions of cyclooxygenase-2 to tumour angiogenesis”. Cancer Metastasis Rev., 2001, 19, 19.

[106] Daniel T.O., Liu H., Morrow J.D., Crews B.C., Marnett L.J.: “Thromboxane A2 is a mediator of cyclooxygenase-2-dependent endothelial migration and angiogenesis”. Cancer Res., 1999, 59, 4574.

[107] Pezzella F., Pastorino U., Tagliabue E., Andreola S., Sozzi G., Gasparini G., et al.: “Non-small-cell lung carcinoma tumor growth without morphological evidence of neo-angiogenesis”. Am. J. Pathol., 1997, 151, 1417.

[108] Maniotis A.J., Folberg R., Hess A., Seftor E.A., Gardner L.M., Pe’er J., et al.: “Vascular channel formation by human melanoma cells in vivo and in vitro: vasculogenic mimicry”. Am. J. Pathol., 1999, 155, 739.

[109] Shirakawa K., Shibuya M., Heike Y., Takashima S., Watanabe I., Konishi F., et al.: “Tumor-infiltrating endothelial cells and endothelial precursor cells in inflammatory breast cancer”. Int. J. Cancer, 2002, 99, 344.

[110] Hendrix M.J., Seftor E.A., Hess A.R., Seftor R.E.:”Vasculogenic mimicry and tumour-cell plasticity: lessons from melanoma”. Nat. Rev. Cancer, 2003, 3, 411.

[111] Shirakawa K., Kobayashi H., Heike Y., Kawamoto S., Brechbiel M.W., Kasumi F., et al.: “Hemodynamics in vasculogenic mimicry and angiogenesis of inflammatory breast cancer xenograft”. Cancer Res., 2002, 62, 560.

[112] Basu G.D., Liang W.S., Stephan D.A., Wegener L.T., Conley C.R, Pockaj B.A., Mukerjee P.: “A novel role for cyclooxygenase-2 in regulating vascular channel formation by human breast cancer cells”. Breast Cancer Res., 2006, 8, R69.

[113] Khuder S.A., Mutgi,A.B.: “Breast cancer and NSAID use: a metaanalysis”. Br. J. Cancer, 2001, 84, 1188.

[114] Egan, K., Stampfer, M., Giovannucci, E., Rosner, B., Colditz, G. Prospective study of regular aspirin use and the risk of breast cancer. J. Natl. Cancer Inst. 1996, (Bethesda), 88, 988.

[115] Rosenberg L., Palmer J.R., Zauber A.G., Warshaver M.E., Stolley P.D., Shapiro S.: “A hypothesis: nonsteroidal anti-inflammatory drugs reduce the incidence of large-bowel cancer”. J. Natl. Cancer Inst., 1991, 83, 355.

[116] Thun M.J., Namboodiri M.M., Heath C.W. Jr.: “Aspirin use and reduced risk of fatal colon cancer”. N. Engl. J. Med., 1991, 325,1593.

[117] Alshafie G.A., Abou-Issa H., Seibert K., Harris R.: “Chemotherapeutic evaluation of celecoxib, a cyclooxygenase-2 inhibitor, in rats mammary tumor model”. Oncol. Rep., 2000, 7, 1377.

[118] Harris R.E., Alshafie G.A., Abou-Issa H., Seibert K.: “Chemoprevention of breast cancer in rats by celecoxib, a cyclooxygenase 2 inhibitor”. Cancer Res. 2000, 60, 2101.

[119] Barnes N.L., Warnberg F., Farnie G., White D., Jiang W., Anderson E., Bundred N.J.: “Cyclooxygenase-2 inhibition: effects on tumour growth, cell cycling and lymphangiogenesis in a xenograft model of breast cancer”. Br. J. Cancer, 2007, 96, 575.

[120] Yoshinaka R., Shibata M.A., Morimoto J., Tanigawa N., Otsuki Y.: “COX-2 inhibitor celecoxib suppresses tumor growth and lung metastasis of a murine mammary cancer”. Anticancer Res., 2006, 26, 4245.

[121] Fabi A., Metro G., Papaldo P., Mottolese M., Melucci E., Carlini P., et al.: “Impact of celecoxib on capecitabine tolerability and activity in pretreated metastatic breast cancer: results of a phase II study with biomarker evaluation”. Cancer Chemother. Pharmacol., 2008, 62, 717.

[122] Canney P. A., Machin M.A., Curto J.: “A feasibility study of the efficacy and tolerability of the combination of Exemestane with the COX-2 in-hibitor Celecoxib in post-menopausal patients with advanced breast cancer”. Eur. J. Cancer, 2006, 42, 2751.

[123] Dirix L.Y., Ignacio J., Nag S., Bapsy P., Gomez H., Raghunadharao D., et al.: “Treatment of advanced hormone-sensitive breast cancer in postmenopausal women with exemestane alone or in combination with celecoxib”. J. Clin. Oncol., 2008, 10, 26, 1253.

[124] Beer T.M., Ryan C.W., Venner P.M., Petrylak D.P., Chatta G.S., Ruether J.D., et al.: “ASCENT(AIPC Study of Calcitriol ENhancing Taxotere) Investigators. Intermittent chemotherapy in patients with metastatic androgen-independent prostate cancer: results from ASCENT, a double-blinded, randomized comparison of high-dose calcitriol plus docetaxel with placebo plus docetaxel”. Cancer, 2008, 112, 326.

[125] Dragovich T., Burris H. 3rd, Loehrer P., Von Hoff D.D., Chow S., Stratton S., et al.: “Gemcitabine plus celecoxib in patients with advanced or metastatic pancreatic adenocarcinoma: results of a phase II trial”. Am. J. Clin. Oncol., 2008, 31, 157.

[126] Agarwala A., Fisher W., Bruetman D., McClean J., Taber D., Titzer M., et al.: “Gefitinib plus celecoxib in chemotherapy-naïve patients with stage IIIB/IV non-small cell lung cancer: a phase II study from the Hoosier Oncology Group”. J. Thorac. Oncol., 2008, 3, 374.

[127] Xiao H., Zhang Q., Lin Y., Reddy B.S., Yang C.S.: “Combination of atorvastatin and celecoxib synergistically induces cell cycle arrest and apoptosis in colon cancer cells”. Int. J. Cancer, 2008, 122, 2115.

[128] Giovanucci E.: “The epidemiology of vitamin D and cancer incidence and mortality: a review (United States)”. Cancer Causes Control, 2005, 16, 83.

[129] Holick M.F.: “Sunlight and vitamin D for bone health and prevention of autoimmune diseases, cancers, and cardiovascular disease”. Am. J. Clin. Nutr., 2004, 80, 1678.

[130] Trang H.M., Cole D.E., Rubin L.A., Pierratos A., Siu S., Vieth R.: “Evidence that vitamin D3 increases serum 25-hydroxyvitamin D more efficiently than does vitamin D2”. Am. J. Clin. Nutr., 1998, 68, 854.

[131] Hollis B.W., Wagner C.L.: “Normal serum vitamin D levels”. N. Engl. J. Med., 2005, 352, 515.

[132] Reichrath J.: “Vitamin D and the skin: an ancient friend, revisited”. Exp. Dermatol., 2007, 16, 618.

[133] Holick M.F.: “The cutaneous photosynthesis of previtamin D3: a unique photoendocrine system”. J. Invest. Dermatol., 1981, 77, 51.

[134] Feskanich D., Ma J., Fuchs C.S., Kirkner G.J., Hankinson S.E., Hollis B.W., Giovannucci E.L.: “Plasma vitamin D metabolites and risk of colorectal cancer in women”. Cancer Epidemiol. Biomarkers Prev., 2004, 13, 1502.

[135] Ohyama Y., Yamasaki T.: “Eight cytochrome P450s catalyze vitamin D metabolism”. Front. Biosci., 2004, 9, 3007.

[136] Hewison M., Zehnder D., Chakraverty R., Adams J.S.: “Vitamin D and barrier function: a novel role for extra-renal 1-hydroxylase”. Mol. Cell En-docrinol., 2004, 215, 31.

[137] Bell N.H.: “Renal and nonrenal 25-hydroxyvitamin D-1-hydroxylases and their clinical significance”. J. Bone Miner. Res., 1998, 13, 350.

[138] Omdahl, J.L., Morris H.A., May B.K.: “Hydroxylase enzymes of the vitamin D pathway: expression, function, and regulation”. Annu. Rev. Nutr., 2002, 22, 139.

[139] Dusso A.S., Brown A.J., Slatopolsky E.: “Vitamin D”. Am. J. Physiol. Renal Physiol., 2005, 289, F8.

[140] Turunen M.M., Dunlop T.W., Carlberg C.: “Selective use of multiple vitamin D response elements underlies the 1 alpha,25-dihydroxyvitamin D3-mediated negative regulation of the human CYP27B1 gene”. Nucleic Acids Res., 2007, 35, 2734.

[141] Zitterman A.: “Vitamin D in preventive medicine: are we ignoring the evidence?” Br. J Nutr., 2003, 89, 552.

[142] Hewison M., Zehnder D., Bland R., Stewart P.M.: “1-Hydroxylase and the action of vitamin D”. J. Mol. Endocrinol., 2000, 25, 141.

[143] Zehnder D., Bland R., Chana R.S., Wheeler D.C., Howie A.J., Williams, M.C., et al.: “Synthesis of 1,25-dihydroxyvitamin D(3) by human endothelial cells is regulated by inflammatory cytokines: a novel autocrine determinant of vascular cell adhesion”. J. Am. Soc. Nephrol., 2002, 13, 621.

[144] Stoffels, K., Overbergh, L., Giulietti, A., Verlinden, L., Bouillon, R., Mathieu, C.: “Immune regulation of 25-hydroxyvitamin-D3-1alphahydroxylase in human monocytes”. J. Bone Miner. Res. 2006, 21, 37.

[145] Overbergh L., Stoffels K., Waer M., Verstuyf A., Bouillon R., Mathieu C.: “Immune regulation of 25-hydroxyvitamin D-1alpha-hydroxylase in human monocytic THP1 cells: mechanisms of interferon-gamma-mediated induction”. J. Clin. Endocrinol. Metab., 2006, 91, 3566.

[146] Stoffels K., Overbergh L., Bouillon R., Mathieu C.: “Immune regulation of 1alpha-hydroxylase in murine peritoneal macrophages: unravelling the IFNgamma pathway”. J. Steroid. Biochem. Mol. Biol., 2007, 103, 567.

[147] Lopez E.R, Zwermann O., Segni M., Meyer G., Reincke M., Seissler J., et al.: “A promoter polymorphism of the CYP27B1 gene is associated with Addison’s disease, Hashimoto’s thyroiditis, Graves’ disease and type 1 diabetes mellitus in Germans”. Eur. J. Endocrinol., 2004, 151, 193.

[148] Fischer D., Seifert M., Becker S., Ludders D., Cordes T., Reichrath J., Friedrich M.: “25-Hydroxyvitamin D3 1alpha-hydroxylase splice variants in breast cell lines MCF-7 and MCF-10”. Cancer Genomics Proteomics, 2007, 4, 295.

[149] Cordes T., Diesing D., Becker S., Fischer D., Diedrich K., Friedrich M.: “Expression of splice variants of 1alpha-hydroxylase in mcf-7 breast cancer cells”. J. Steroid. Biochem. Mol. Biol., 2007, 103, 326.

[150] Barreto A.M., Schwartz G.G., Woodruff R., Cramer S.D.: “25-Hydroxyvitamin D3, the prohormone of 1,25-dihydroxyvitamin D3, inhibits the proliferation of primary prostatic epithelial cells”. Cancer Epidemiol. Biomarkers Prev., 2000, 9, 265.

[151] Schwartz G.G., Whitlatch L.W., Chen T.C., Lokeshwar B.L., Holick M.F.: “Human prostate cells synthesize 1,25-dihydroxyvitamin D3 from 25-hydroxyvitamin D3”. Cancer Epidemiol. Biomarkers Prev., 1998, 7, 391.

[152] Tangpricha V., Flanagan J.N., Whitlatch L.W., Tseng C.C., Chen T.C., Holt P.R., et al.: “F. 25-Hydroxyvitamin D-1-hydroxylase in normal and malignant colon tissue”. Lancet, 2001, 357, 1673.

[153] Bareis P., Bises G., Bischof M.G., Cross H.S., Peterlik M.: “25-hydroxy-vitamin D metabolism in human colon cancer cells during tumor progression”. Biochem. Biophys. Res. Commun., 2001, 285, 1012.

[154] Ogunkolade B.W., Boucher B.J., Fairclough P.D., Hitman G.A., Dorudi S., Jenkins P. J., Bustin S.A.: “Expression of 25-hydroxyvitamin D-1--hydroxylase mRNA in individuals with colorectal cancer”. Lancet 2002, 359, 1831.

[155] Friedrich M., Diesing D., Cordes T., Fischer D., Becker S., Chen T.C., et al.: “Analysis of 25-hydroxyvitamin D3-1alpha-hydroxylase in normal and malignant breast tissue”. Anticancer Res., 2006, 26, 2615.

[156] Garland C.F., Comstock G.W., Garland F.C., Helsing K.J., Shaw E.K., Gorham E.D.: “Serum 25-hydroxyvitamin D and colon cancer: eight-year prospective study”. Lancet, 1989, 2, 1176.

[157] Holt P. R., Arber N., Halmos B., Forde K., Kissileff H., McGlynn K. A., et al.: “Colonic epithelial cell proliferation decreases with increasing levels of serum 25-hydroxy vitamin D”. Cancer Epidemiol. Biomarkers Prev., 2002, 11, 113.

[158] Lowe L.C., Guy M., Mansi J.L., Peckitt C., Bliss J., Wilson R.G., Colston K.W.: “Plasma 25-hydroxy vitamin D concentrations, vitamin D receptor genotype and breast cancer risk in a UK Caucasian population”. Eur. J. Cancer, 2005, 41, 1164.

[159] Berube S., Diorio C., Verhoek-Oftedahl W., Brisson J.: “Vitamin D, calcium and mammographic breast densities”. Cancer Epidemiol. Biomarkers Prev., 2004, 13, 1466.

[160] Huang D.C., Papavasiliou V., Rhim J.S., Horst R.L., Kremer R.: “Targeted disruption of the 25-hydroxyvitamin D3 1alpha-hydroxylase gene in ras-transformed keratinocytes demonstrates that locally produced 1alpha,25-dihydroxyvitamin D3 suppresses growth and induces differentiation in an autocrine fashion”. Mol. Cancer Res., 2002, 1, 56.

[161] Segersten U., Holm P.K., Björklund P., Hessman O., Nordgren H., Binderup L., et al.: “25-Hydroxyvitamin D3 1alpha-hydroxylase expression in breast cancer and use of non-1alpha-hydroxylated vitamin D analogue”. Breast Cancer Res., 2005, 7, 980.

[162] Agic A., Xu H., Altgassen C., Noack F., Wolfler M.M., Diedrich K., et al.: “Relative expression of 1,25-dihydroxyvitamin D3 receptor, vitamin D 1 alpha-hydroxylase, vitamin D 24-hydroxylase, and vitamin D 25-hydroxylase in endometriosis and gynecologic cancers”. Reprod. Sci., 2007, 14, 486.

[163] Friedrich M., Rafi L., Mitschele T., Tilgen W., Schmidt W., Reichrath J.: “Analysis of the vitamin D system in cervical carcinomas, breast cancer and ovarian cancer”. Recent Results Cancer Res., 2003, 164, 39.

[164] Hewison M., Kantorovich V., Liker H.R., van Herle A.J., Cohan P., Zehnder D., Adams J.S.: “Vitamin D-mediated hypercalcemia in lymphoma: evidence for hormone production by tumoradjacent macrophages”. J. Bone Miner. Res., 2003, 18, 579.

[165] Evans K.N., Taylor H., Zehnder D., Kilby M.D., Bulmer J.N., Shah F., et al.: Increased expression of 25-hydroxyvitamin D-1-hydroxylase in dysgerminomas: a novel form of humoral hypercalcemia of malignancy. Am. J. Pathol. 2004, 165, 807.

[166] Townsend K., Banwell C.M., Guy M., Colston K.W., Mansi J. L., Stewart P. M., et al.: “Autocrine metabolism of vitamin D in normal and malignant tissue”. Clin. Cancer Res., 2005, 11, 3579.

[167] Ainsleigh H.G.: “Beneficial effects of sun exposure on cancer mortality”. Prev. Med., 1993, 22, 132.

[168]Gorham E.D., Garland F.C., Garland C.F.: “Sunlight and breast cancer incidence in the USSR”. Int. J. Epidemiol. 1990, 19, 820.

[169] Garland F.C., Garland C.F., Gorham E.D., Young J.F.: “Geographic variation in breast cancer mortality in the United States: a hypothesis involving exposure to solar radiation”. Prev. Med. 1990, 19, 614.

[170] Grant W.B.: “An estimate of premature cancer mortality in the U.S. due to inadequate doses of solar ultraviolet-B radiation”. Cancer 2002, 94, 1867.

[171] Kemmis C.M., Salvador S.M., Smith K.M., Welsh J.: “Human mammary epithelial cells express CYP27B1 and are growth inhibited by 25-hy-droxyvitamin D-3, the major circulating form of vitamin D-3”. J. Nutr., 2006, 136, 887.

[172] Holick M.F., Siris E.S., Binkley N., Beard M.K., Khan A., Katzer J.T., et al.: “Prevalence of vitamin D inadequacy among postmenopausal women. North American women receiving osteoporosis therapy”. J. Clin. Endocrinol. Metabo., 2005, 90, 3215.

[173] Sowers M.R., Wallace R.B., Hollis B.W., Lemke J.H.: “Parameters related to 25-OH-D levels in a population-based study of women”. Am. J. Clin. Nutr. 1986, 43, 621.

[174] Diesing D., Cordes T., Fischer D., Diedrich K., Friedrich M.: “Vitamin D—metabolism in the human breast cancer cell line MCF-7”. Anticancer Res., 2006, 26, 2755.

[175] Sunn K.L., Cock T.A., Crofts L.A., Eismann J.A., Gardiner E.M.: “Novel N-terminal variant of human VDR”. Mol. Endocrinol., 2001, 15, 1599.

[176] Tsai M.J., O’Malley B.W.: “Molecular mechanisms of action of steroid/thyroid receptor superfamily members”. Annu. Rev. Biochem., 1994, 63, 451.

[177] Nemere I., Szego C.M.: “Early actions of parathyroid hormone and 1,25-dihydroxycholecalciferol on istolated epithelial cells from rat intestine”. Endocrinology, 1981, 108, 1450.

[178] Studzinski G.P., McLane J.A., Uskokovic M.R.: “Signaling pathways for vitamin D-induced differentiation: implications for therapy of proliferative and neoplastic diseases”. Crit. Rev. Eukaryot. Gene Expr., 1993, 4, 279.

[179] Marcinkowska E., Wiedlocha A., Radzikowsi C.: “1,25-dihydroxyvitamin D3 induced activation and subsequent nuclear translocation of MAPK is upstream regulated by PKC in HL-60 cells”. Biochem. Biophys. Res. Commun., 1997, 241, 410.

[180] Marcinkowska E., Wiedlocha A., Radzikowski C.: “Evidence that phosphatidylinositol 3-kinase and p70S6Kprotein are involved in differentiation of HL-60 cells induced by calcitriol”. Anticancer Res., 1998, 18, 3507.

[181] Marcinkowska E.: “Evidence that activation of MEK1,2/erk1,2 signal transduction pathway is necessary for calcitriol-induced differentiation of HL-60 cells”. Anticancer Res., 2001, 21, 499.

[182] Mehta R.G., Mehta R.R.: “Vitamin D and cancer.” J. Nutr. Biochem., 2002, 13, 252.

[183] Boland R., De Boland A.R., Buitrago C., Morelli S., Santillan G., Vazque G., et al.: “Non-genomic stimulation of tyrosine phosphorylation cascades by 1,25(OH)(2)D(3) by VDR-dependent and –independent mechanisms in muscle cells”. Steroids, 2002, 67, 477-482.

[184] Marcinkowska E., Wiedlocha A.: “Steroid signal transduction activated at the cell membrane: from plants to animal”. Acta Biochimica Polonica, 2002, 49, 735.

[185] Colston K.W., Berger U., Coombes R.C.: “Possible role for vitamin D in controlling breast cancer cell proliferation”. Lancet, 1989, 1, 188.

[186] James S.Y., Mackay A.G., Colston K.W.: “Vitamin D derivatives in combination with 9-cis retinoic acid promote active cell death in breast cancer cells”. J. Mol. Endocrinol., 1995, 14, 391.

[187] Welsh J.E.: “Induction of apoptosis in breast cancer cells in response to vitamin D and antiestrogens”. Biochem. Cell. Biol., 1995, 72, 537.

[188] Berger U., Wilson P., McClelland R. A., Colston K., Haussler M.R., Pike J. W., Coombes R.C.: “Immunocytochemical determination of estrogen receptor, progesterone receptor, and 1,25-dihydroxyvitamin D3 receptor in breast cancer and relationship to prognosis”. Cancer Res., 1991, 51, 239.

[189] Welsh J.: “Targets of vitamin D receptor signaling in the mammary gland”. J. Bone Miner. Res. 2007, 22, V86.

[190] Uitterlinden A.G., Fang Y., Van Meurs J.B., Pols H.A., Van Leeuwen J.P.: “Genetics and biology of vitamin D receptor polymorphisms”. Gene, 2004, 338 143.

[191] Guy M., Lowe L.C., Bretherton-Watt D., Mansi J.L., Peckitt C., Bliss, J., et al.: “Vitamin D receptor gene polymorphisms and breast cancer risk”. Clin. Cancer Res., 2004, 10, 5472.

[192] Curran J.E., Vaughan T., Lea R.A., Weinstein S.R., Morrison N.A., Griffiths L.R.: “Association of A vitamin D receptor polymorphism with sporadic breast cancer development”. Int. J. Cancer, 1999, 83, 723.

[193] Chen W.Y., Bertone-Johnson E.R., Hunter D.J., Willett W.C., Hankinson S.E.: “Associations between polymorphisms in the vitamin D receptor and breast cancer risk”. Cancer Epidemiol. Biomarkers Prev. 2005, 14, 2335.

[194] Sinotte M., Rousseau F., Ayotte P., Dewailly E., Diorio C., Giguere Y., et al.: “Vitamin D receptor polymorphisms (FokI, BsmI) and breast cancer risk: association replication in two case-control studies within French Canadian population”. Endocr. Relat. Cancer, 2008, 15, 975.

[195] Trabert B., Malone K.E., Daling J.R., Doody D.R., Bernstein L., Ursin G., M et al.: “Vitamin D receptor polymorphisms and breast cancer risk in a large population-based case-control study of Caucasian and African-American women”. Breast Cancer Res., 2007, 9, R84.

[196] Lundin A.C., Soderkvist P., Eriksson B., Bergman-Jungestrom M., Wingren S.: “Association of breast cancer progression with a vitamin D receptor gene polymorphism. South-East Sweden Breast Cancer Group”. Cancer Res., 1999, 59, 2332.

[197] Ruggiero M., Pacini S., Aterini S., Fallai C., Ruggiero C., Pacini P.: “Vitamin D receptor gene polymorphism is associated with metastatic breast cancer”. Oncol. Res., 1998, 10, 43.

[198] Dunning A.M., McBride S., Gregory J., Durocher F., Foster N.A., Healy C.S., et al.: “No association between androgen or vitamin D receptor gene polymorphisms and risk of breast cancer”. Carcinogenesis, 1999, 20, 2131.

[199] Newcomb P.A., Kim H., Trentham-Dietz A., Farin F., Hunter D., Egan K.M.: “Vitamin D receptor polymorphism and breast cancer risk”. Cancer Epidemiol. Biomarkers Prev., 2002, 11, 1503.

[200] Cui Y., Rohan T.E.: “Vitamin D, calcium, and breast cancer risk: a review”. Cancer Epidemiol. Biomarkers Prev., 2006, 15, 1427.

[201] McCullough M.L., Stevens V.L., Diver W.R., Feigelson H.S., Rodriguez C., Bostick R.M., et al.: “Vitamin D pathway gene polymorphisms, diet, and risk of postmenopausal breast cancer: a nested case-control study”. Breast Cancer Res., 2007, 9, R9.

[202] Cashman K.D.: “Calcium intake, calcium bioavailability and bone health”. Br. J. Nutr., 2002, 87, S169.

[203] Welsh J.: “Vitamin D and breast cancer: insights from animal models”. Am. J. Clin. Nutr., 2004, 80, 1721.

[204] Mantell D.J., Owens P. E., Bundred N.J., Mawer E.B., Canfield A.E.: “1,25-Dihydroxyvitamin D(3) inhibits angiogenesis in vitro and in vivo”. Circ. Res., 2000, 87, 214–2.

[205] Saez S., Falette N., Guillot C., Meggouh F., Lefebvre, M.F., Crepin, M.: “William L. McGuire Memorial Symposium. 1,25(OH)2D3 modulation of mammary tumor cell growth in vitro and in vivo”. Breast Cancer Res. Treat., 1993, 27, 69.

[206] Eisman J.A., Sutherland R.L., McMenemy M.L., Fragonas J.C., Musgrove E.A., Pang G.Y.: “Effects of 1,25-dihydroxyvitamin D3 on cell-cycle kinetics of T 47D human breast cancer cells”. J. Cell. Physiol., 1989, 138, 611.

[207] Jacobson E.A., James K.A., Newmark H.L., Carroll K.K.: “Effects of dietary fat, calcium, and vitamin D on growth and mammary tumorigenesis induced by 7,12-dimethylbenz(a)anthracene in female Sprague-Dawley rats”. Cancer Res., 1989, 49, 6300.

[208] Xue L., Lipkin M., Newmark H., Wang J.: “Influence of dietary calcium and vitamin D on diet-induced epithelial cell hyperproliferation in mice”. J. Natl. Cancer Inst., 1999, 91, 176.

[209] John E.M., Schwartz G.G., Dreon, D.M., Koo J.: “Vitamin D and breast cancer risk: the NHANES I epidemiologic follow-up study, 1971-1975 to 1992. National Health and Nutrition Examination Survey”. Cancer Epidemiol. Biomarkers Prev., 1999, 8, 399.

[210] Knight J.A., Lesosky M., Barnett H., Raboud, J.M., Vieth R.: “Vitamin D and reduced risk of breast cancer: A population-based control study”. Cancer Epidemiol. Biomarkers Prev. 2007, 16, 422.

[211] McCullough M.L., Rodriguez C., Diver W.R., Feigelson H.S., Stevens V.L., Thun M.J., Calle E.E.: “Dairy, calcium, and vitamin D intake and postmenopausal breast cancer risk in the Cancer Prevention Study II Nutrition Cohort. Cancer Epidemiol”. Biomarkers Prev., 2005, 14, 2898.

[212] Rossi M., McLaughlin J.K., Lagiou P., Bosetti C., Talamini R., Lipworth L., et al.: “Vitamin D intake and breast cancer risk: a case-control study in Italy”. Ann. Oncol., 2009, 20, 374.

[213] Frazier A.L., Ryan C.T., Rockett H., Willett W.C., Colditz G.A.: “Adolescent diet and risk of breast cancer”. Breast Cancer Res., 2003, 5, R59.

[214] Frazier A.L., Li L., Cho E., Willett W.C., Colditz G.A.: “Adolescent diet and risk of breast cancer”. Cancer Causes Control, 2004, 15, 73.

[215] Gissel T., Rejnmark L., Mosekilde L., Vestergaard P.: “Intake of vitamin D and risk of breast cancer—a meta-analysis”. J. Steroid. Biochem. Mol. Biol., 2008, 111, 195.

[216] Hiatt R.A., Krieger N., Lobaugh B., Drezner M.K., Vogelman J.H., Orentreich N.: “Prediagnostic serum vitamin D and breast cancer”. J. Natl. Cancer Inst., 1998, 90, 461.

[217] Bertone-Johnson E.R., Chen W.Y., Holick M.F., Hollis B.W., Colditz G.A., Willett W.C., Hankinson S.E.: “Plasma 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D and risk of breast cancer”. Cancer Epidemiol. Biomarkers Prev., 2005, 14, 1991.

[218] Mawer E.B., Walls J., Howell A., Davies M., Ratcliffe W.A., Bundred N.J.: “Serum 1,25-dihydroxyvitamin D may be related inversely to disease activity in breast cancer patients with bone metastases”. J. Clin. Endocrinol. Metab., 1997, 82, 118.

[219] Whitfield J.F., Boynton A.L., MacManus J.P., Sikorska M., Tsang B.K.: “The regulation of cell proliferation by calcium and cyclic AMP”. Mol. Cell Biochem., 1979, 27, 155.

[220] Mathiasen I.S., Sergeev I.N., Bastholm L., Elling F., Norman A.W., Jaattela M.: “Calcium and calpain as key mediators of apoptosis-like death induced by vitamin D compounds in breast cancer cells”. J. Biol. Chem., 2002, 277, 30738.

[221] Sergeev I.N.: “Calcium as a mediator of 1,25-dihydroxyvitamin D3-induced apoptosis”. J. Steroid. Biochem. Mol. Biol., 2004, 89, 419.

[222] McGrath C.M., Soule H.D.: “Calcium regulation of normal human mammary epithelial cell growth in culture”. In Vitro, 1984, 20, 652.

[223] Russo J., Russo I.H.: “The pathway of neoplastic transformation of human breast epithelial cells”. Radiat. Res., 2001, 155, 151.

[224] Boyapati S.M., Shu X.O., Jin F., Dai Q., Ruan Z., Gao Y.T., Zheng W.: “Dietary calcium intake and breast cancer risk among Chinese women in Shanghai”. Nutr. Cancer 2003, 46, 38.

[225] Wark J.D., Larkins R.G., Eisman J.A., Wilson K.R.: “Regulation of 25-hydroxyvitamin-D-la-hydroxylase in chick isolated renal tubules: effects of prostaglandin E2, frusemide and acetylsalicylate.” Clin. Sci., 1981, 62, 53.

[226] Hayes M.E., Rai A., Cooper R.G., Bayley D., Freemont A.J., Mawer E.B.: “Inhibition by prostaglandin E1 and E2 of 1,25-dihydroxyvitamin D3 synthesis by synovial fluid macrophages from arthritic joints”. Ann. Rheum. Dis., 1992, 51, 632.

[227] Miller G.J.: “Vitamin D and prostate cancer: biologic interactions and clinical potentials”. Cancer Metastasis Rev., 1998, 17, 353.

[228] Konety B.R., Getzenberg R.H.: “Vitamin D and prostate cancer”. Urol. Clin. North Am., 2002, 29, 95.

[229] Zhuang S.H., Burnstein K.L.: “Antiproliferative effect of 1a,25-dihydroxyvitamin D3 in human prostate cancer cell line LNCaP involves reduction of cyclin-dependent kinase 2 activity and persistent G1 accumulation”. Endocrinology, 1998, 139, 1197.

[230] Moreno J., Krishnan A.V., Swami S., Nonn L., Peehl D.M., Feldman D.: “Regulation of prostaglandin metabolism by calcitriol attenuates growth stimulation in prostate cancer cells”. Cancer Res. 2005, 65, 7917.

Abstracted / indexed in

Science Citation Index Expanded (SciSearch) Created as SCI in 1964, Science Citation Index Expanded now indexes over 9,500 of the world’s most impactful journals across 178 scientific disciplines. More than 53 million records and 1.18 billion cited references date back from 1900 to present.

Biological Abstracts Easily discover critical journal coverage of the life sciences with Biological Abstracts, produced by the Web of Science Group, with topics ranging from botany to microbiology to pharmacology. Including BIOSIS indexing and MeSH terms, specialized indexing in Biological Abstracts helps you to discover more accurate, context-sensitive results.

Google Scholar Google Scholar is a freely accessible web search engine that indexes the full text or metadata of scholarly literature across an array of publishing formats and disciplines.

JournalSeek Genamics JournalSeek is the largest completely categorized database of freely available journal information available on the internet. The database presently contains 39226 titles. Journal information includes the description (aims and scope), journal abbreviation, journal homepage link, subject category and ISSN.

Current Contents - Clinical Medicine Current Contents - Clinical Medicine provides easy access to complete tables of contents, abstracts, bibliographic information and all other significant items in recently published issues from over 1,000 leading journals in clinical medicine.

BIOSIS Previews BIOSIS Previews is an English-language, bibliographic database service, with abstracts and citation indexing. It is part of Clarivate Analytics Web of Science suite. BIOSIS Previews indexes data from 1926 to the present.

Journal Citation Reports/Science Edition Journal Citation Reports/Science Edition aims to evaluate a journal’s value from multiple perspectives including the journal impact factor, descriptive data about a journal’s open access content as well as contributing authors, and provide readers a transparent and publisher-neutral data & statistics information about the journal.

Submission Turnaround Time