Analysis of the Vitamin D System in Cervical Carcinomas, Breast Cancer and Ovarian Cancer

1,25-Dihydroxyvitamin D3(1,(OH)2D3) is the biologically active metabolite of vitamin D and has been shown to regulate the growth of various cell types. There are two principal enzymes involved in the formation of circulating 1,(OH)2D3from vitamin D, the vitamin D 25-hydroxylase (25-OHase) and the 1a-hydroxylase (1α-OHase). Recently, extrarenal activity of 1a-OHase has been reported in various cell types. The aim of this study was to analyze expression of VDR and the main enzymes involved in the synthesis and metabolism of calcitriol in gynecological malignancies and corresponding normal tissue. Expression of VDR, 25-OHase, 1α-OHase, and 24-OHase was analyzed in breast carcinomas (BC), ovarian cancer (OC), cervix carcinomas (CC) and normal corresponding tissues using real-time PCR and specific hybridization probes as well as using immunohistochemistry. RNA for VDR, 1α-OHase, 24-OHase and 25-OHase was up-regulated in breast cervical and ovarian carcinomas as compared to normal tissue. VDR immunoreactivity was increased in breast and ovarian cancer and in cervix carcinomas as compared to normal corresponding tissue. Our findings indicate that cervical carcinomas, breast cancer and ovarian cancer may be considered as potential targets for prevention or therapy with new vitamin D analogs that exert little or no calcemic side effects or by pharmacological modulation of 1,(OH)2D3synthesis and metabolism in these tumor cells. Preview Unable to display preview. Download preview PDF. Similar content being viewed by others

Smith EL, Walworth NC, Holick MF (1986) Effect of 1,25-dihydroxyvitamin D3on the morphologic and biochemical differentiation of cultured human epidermal cells. J Invest Dermatol 86:709–714 Bikle DD, Pillai S (1993) Vitamin D, calcium and epidermal differentiation. Endocrine Rev 14:3–19 Stumpf WE, Sar M, Reid FA, Tanaka Y, DeLuca HF (1979) Target cells for 1,25-dihydroxyvitamin D3in intestinal tract, stomach, kidney, skin, pituitary and parathyroid. Science 209:1189–1190 Baker AR, McDonnell DP, Hughes M (1988) Cloning and expression of full-length cDNA encoding human vitamin D receptor. Proc Natl Acad Sci U S A 85:3294–3298 Kliewer SA, Umesono K, Mangelsdorf DJ, Evans RM (1992) Retinoic X receptor interacts with nuclear receptors in retinoic acid, thyroid hormone and vitamin D3signalling. Nature 355:446–449 Evans RM (1988) The steroid and thyroid hormone receptor superfamily. Science 240:889–895 Majewski S, Skopinska M, Bollag W, Jablonska S (1994) Combination of isotretinoin and calcitriol for precancerous and cancerous skin lesions. Lancet 344:1510–1511 Henry HL (1992) Vitamin D hydroxylase. J Cell Biochem 49:4–9 Nebert DW, Gonzalez FJ (1987) P450 genes: structure, evolution, and regulation. Annu Rev Biochem 56:945–993 Jones G, Ramshaw H, Zhang A, Cook R, Byford V, White J, Petkovich M (1999) Expression and activity of vitamin D-metabolizing cytochrome P450s (CYP1a and CYP24) in human non-small cell lung carcinomas. Endocrinology 140:3303–3310 Tangpricha V, Flanagan JN, Whitlatch LW, Tseng CC, Chen TC, Holt PR, Lipkin MS, Holick MF (2001) 25-hydroxyvitamin D-1alpha-hydroxylase in normal and malignant colon tissue. Lancet 357(9269):1673–1674 Friedrich M, Villena-Heinsen C, Axt-Fliedner R, Meyberg R, Tilgen W, Schmidt W, Reichrath J (2002) Analysis of 25-Hydroxyvitamin D3–1a-hydroxylase in cervical tissue. Anticancer Res 22:183–186 Author information Authors and Affiliations Editor information Editors and Affiliations Rights and permissions Copyright information © 2003 Springer-Verlag Berlin Heidelberg About this paper Cite this paper Friedrich, M., Rafi, L., Mitschele, T., Tilgen, W., Schmidt, W., Reichrath, J. (2003). Analysis of the Vitamin D System in Cervical Carcinomas, Breast Cancer and Ovarian Cancer. In: Reichrath, J., Tilgen, W., Friedrich, M. (eds) Vitamin D Analogs in Cancer Prevention and Therapy. Recent Results in Cancer Research, vol 164. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-55580-0_17 Download citation DOI: https://doi.org/10.1007/978-3-642-55580-0_17 Publisher Name: Springer, Berlin, Heidelberg Print ISBN: 978-3-642-62435-3 Online ISBN: 978-3-642-55580-0 eBook Packages: Springer Book Archive

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