Vitamin D co-regulates cell proliferation, differentiation and apoptosis, the processes that are disturbed in cancer tissues. It acts through the vitamin D nuclear receptor (VDR) that binds to DNA in the regulatory sequences of the target genes. As the kidney is one of the key organs for vitamin D metabolism and action, we analyzed VDR expression and its DNA binding activity in human renal clear cell cancer. 24 tumors, 24 controls that were excised from the opposite pole of the same kidney and 7 controls originating from kidneys without cancer were examined. Independently of tumor grading neither Northern blots nor immunoblotting demonstrated statistically significant differences of the mean VDR mRNA and protein amounts, respectively, in the cancer as compared to both control types. In contrast, the amount of VDR-DNA complexes was lower in 52.2% of the tumors in comparison to their corresponding controls. After normalization against VDR receptor protein amount in 34.8% of the tumors VDR-DNA binding was at least 3–4 times weaker than in the controls. However, the expression of vitamin D-dependent P21 gene on the mRNA level was not decreased in these cancers. It remains to be elucidated if altered VDR function due to its impaired binding to DNA contributes to the process of tumorigenesis, and what potential vitamin D-dependent mechanisms are involved in this process.

1.
Celli A, Treves C, Stio M: Vitamin D receptor in SH-SY5Y human neuroblastoma cells and effect of 1,25-dihydroxyvitamin D3 on cellular proliferation. Neurochem Int 1999;34:117–124.
2.
Rashid SF, Moore JS, Walker E, Driver PM, Engel J, Edwards CE, Brown G, Uskokovic MR, Campbell MJ: Synergistic growth inhibition of prostate cancer cells by 1α,25-dihydroxyvitamin D(3) and its 19-nor-hexafluoride analogs in combination with either sodium butyrate or trichostatin A. Oncogene 2001;20:1860–1872.
3.
Zhuang SH, Burnstein KL: Antiproliferative effect of 1α,25-dihydroxyvitamin D3 in human prostate cancer cell line LNCaP involves reduction of cyclin-dependent kinase 2 activity and persistent G1 accumulation. Endocrinology 1998;139:1197–1207.
[PubMed]
4.
James SY, Mackay AG, Colston KW: Effects of 1,25-dihydroxyvitamin D3 and its analogues on induction of apoptosis in breast cancer cells. J Steroid Biochem Mol Biol 1996;58:395–401.
5.
Blutt SE, McDonnel TJ, Polek TC, Weigel NL: Calcitriol-induced apoptosis in LNCaP cells is blocked by overexpression of Bcl-2. Endocrinology 2000;141:10–17.
[PubMed]
6.
Umesono K, Murakami KK, Thompson CC, Evans RM: Direct repeats as selective response element for the thyroid hormone, retinoic acid, and vitamin D3 receptors. Cell 1991;65:1255–1266.
[PubMed]
7.
Carlberg C, Bendik I, Wyss A, Meier E, Sturzenbecker LJ, Grippo JF, Hunziker W: Two nuclear signalling pathways for vitamin D. Nature 1993;361:657–660.
[PubMed]
8.
Colnot S, Lambert M, Blin C, Thomasset M, Perret C: Identification of DNA sequences that bind retinoid X receptor-1,25(OH)2D3-receptor heterodimers with high affinity. Mol Cell Endocrinol 1995;113:89–98.
9.
Liu M, Lee MH, Cohen M, Bommakanti M, Freedman LP: Transcriptional activation of the Cdk inhibitor p21 by vitamin D3 leads to the induced differentiation of the myelomonocytic cell line U937. Genes Dev 1996;10:142–153.
[PubMed]
10.
Elstner E, Linker-Israeli M, Said J, Umiel T, de Vos S, Shintaku IP, Heber D, Binderup L, Uskokovic M, Koeffler HP: 20-epi-vitamin D3 analogues: A novel class of potent inhibitors of proliferation and inducers of differentiation of human breast cancer cell lines. Cancer Res 1995;55:2822–2830.
11.
Tanaka H, Abe E, Miyaura C, Kuribayashi T, Konno K, Nishii Y, Suda T: 1,25-Dihydroxycholecalciferol and a human myeloid leukaemia cell line (HL-60). Biochem J 1982;204:713–719.
12.
Shiina Y, Abe E, Miyaura C, Tanaka H, Yamada S, Ohmori M, Nakayama K, Takayama H, Matsunaga I, Nishii Y, DeLuca HF, Suda T: Biological activity of 24,24-difluoro-1α,25-dihydroxyvitamin D3 and 1α, 25-dihydroxyvitamin D3–26,23-lactone in inducing differentiation of human myeloid leukemia cells. Arch Biochem Biophys 1983;220:90–94.
13.
Campbell MJ, Gombart AF, Kwok SH, Park S, Koeffler HP: The anti-proliferative effects of 1α,25(OH)2D3 on breast and prostate cancer cells are associated with induction of BRCA1 gene expression. Oncogene 2000;19:5091–5097.
14.
Yabushita H, Hirata M, Noguchi M, Nakanishi M: Vitamin D receptor in endometrial carcinoma and the differentiation-inducing effect of 1,25-dihydroxyvitamin D3 on endometrial carcinoma cell lines. J Obstet Gynaecol Res 1996;22:529–539.
15.
Evans SR, Soldatenkov V, Shchepotin EB, Bogrash E, Shchepotin IB: Novel 19-nor-hexafluoride vitamin D3 analog (Ro 25-6760) inhibits human colon cancer in vitro via apoptosis. Int J Oncol 1999;14:979–985.
16.
Evans SR, Houghton AM, Schumaker L, Brenner RV, Buras RR, Davoodi F, Nauta RJ, Shabahang M: Vitamin D receptor and growth inhibition by 1,25-dihydroxyvitamin D3 in human malignant melanoma cell lines. J Surg Res 1996;61:127–133.
17.
Buras RR, Schumaker LM, Davoodi F, Brenner RV, Shabahang M, Nauta RJ, Evans SR: Vitamin D receptors in breast cancer cells. Breast Cancer Res Treat 1994;31:191–202.
18.
Magrassi L, Bono F, Milanesi G, Butti G: Vitamin D receptor expression in human brain tumors. J Neurosurg Sci 1992:36:27–30.
19.
Cross HS, Bajna E, Bises G, Genser D, Kallay E, Potzi R, Wenzl E, Wrba F, Roka R, Peterlik M: Vitamin D receptor and cytokeratin expression may be progression indicators in human colon cancer. Anticancer Res 1996;16:2333–2337.
20.
Kane KF, Langman MJ, Williams GR: 1,25-Dihydroxyvitamin D3 and retinoid X receptor expression in human colorectal neoplasms. Gut 1995;36:255–258.
21.
Thomas MG, Sylvester PA, Newcomb P, Longman RJ: Vitamin D receptor expression in colorectal cancer. J Clin Pathol 1999;52:181–183.
22.
Nagakura K, Abe E, Suda T, Hayakawa M, Nakamura H, Tazaki H: Inhibitory effect of 1,25-dihydroxyvitamin D3 on the growth of renal carcinoma cell line. Kidney Int 1986;29:834–840.
23.
Trydal T, Bakke A, Aksnes l, Aarskog D: 1,25-Dihydroxyvitamin D3 receptor measurement in primary renal cell carcinomas and autologous normal kidney tissue. Cancer Res 1988;48:2458–2461.
24.
Verdorfer I, Hobisch A, Hittmair A, Duba HC, Bartsch G, Utermann G, Erdel M: Cytogenetic characterization of 22 human renal cell tumors in relation to a histopathological classification. Cancer Genet Cytogenet 1999;111:61–70.
25.
Chomczynski P, Sacchi N: Single-step method of RNA isolation by acid guanidinum thiocyanate-phenol-chloroform extraction. Anal Biochem 1987;162:156–159.
[PubMed]
26.
Kane KF, Langman MJ, Williams GR: Antiproliferative responses of two human colon cancer cell lines to vitamin D3 are differently modified by 9-cis-retinoic acid. Cancer Res 1996;56:623–632.
[PubMed]
27.
Ranjan M, Wong J, Shi Y-B: Transcriptional repression of Xenopus TRβ gene is mediated by a thyroid hormone response element located near the start site. J Biol Chem 1994;269:24699–24705.
28.
Kumar R, Schaefer J, Grande JP, Roche PC: Immunolocalization of calcitriol receptor, 24-hydroxylase cytochrome P-450, and calbindin D28k in human kidney. Am J Physiol 1994;266:F477–F485.
29.
Puzianowska-Kuznicka M, Nauman A, Madej A, Tanski Z, Cheng S-Y, Nauman J: Expression of thyroid hormone receptors is disturbed in human renal clear cell carcinoma. Cancer Lett 2000;155:145–152.
30.
Fujioka T, Suzuki Y, Okamoto T, Matsushita N, Hasegawa M, Omor S: Prevention of renal cell carcinoma by active vitamin D3. World J Surg 2000;24:1205–1210.
31.
Fujioka T, Hasegawa M, Ishikura K, Matsuhita Y, Sato M, Tanji S: Inhibition of tumor growth and angiogenesis by vitamin D3 agents in murine renal cell carcinoma. J Urol 1998;160:247–251.
[PubMed]
32.
Kamiya Y, Puzianowska-Kuznicka M, McPhie P, Nauman J, Cheng S-Y, Nauman A: Expression of mutant thyroid hormone nuclear receptors is associated with human renal clear cell carcinoma. Carcinogenesis 2002;23:25–33.
[PubMed]
33.
Puzianowska-Kuznicka M, Krystyniak A, Madej A, Cheng S-Y, Nauman J: Functionally impaired thyroid hormone receptor mutants are present in thyroid papillary cancer. J Clin Endocr Metab 2002;87:1120–1128.
[PubMed]
34.
Miller CW, Morosetti R, Campbell MJ, Mendoza S, Koeffler HP: Integrity of the 1,25-dihydroxyvitamin D3 receptor in bone, lung, and other cancers. Mol Carcinog 1997;19:254–257.
35.
Chemeris G, Loktinov A, Rempel A, Schwarz M, Bannasch P: Elevated content of p53 protein in the absence of p53 gene mutations as a possible prognostic marker for human renal cell tumors. Virchows Arch 1995;426:563–569.
36.
Uchida T, Wada C, Shitara T, Egawa S, Mashimo S, Koshiba K: Infrequent involvement of p53 mutations and loss of heterozygosity of 17p in the tumorigenesis of renal cell carcinoma. J Urol 1993;150:1298–1301.
[PubMed]
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