Expression of VDR and CYP24A1 mRNA in human tumors

• Published in: Cancer chemotherapy and pharmacology 2006-02, Vol.57 (2), p.234-240
• Main Authors: ANDERSON, Mark G, NAKANE, Masaki, XIAOAN RUAN, KROEGER, Paul E, WU-WONG, J. Ruth
• Format: Article
• Language: English
• Subjects: Antineoplastic agents; Biological and medical sciences; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Calcitriol - metabolism; Colonic Neoplasms - genetics; Colonic Neoplasms - pathology; DNA - biosynthesis; Down-Regulation; Female; Gene Expression Profiling; Humans; Kidneys; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Medical sciences; Nephrology. Urinary tract diseases; Ovarian Neoplasms - genetics; Ovarian Neoplasms - pathology; Pharmacology. Drug treatments; Receptors, Calcitriol - biosynthesis; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - biosynthesis; Signal Transduction; Steroid Hydroxylases - biosynthesis; Steroid Hydroxylases - metabolism; Tumor Cells, Cultured; Urinary system involvement in other diseases. Miscellaneous; Vitamin D3 24-Hydroxylase
• ISSN: 0344-5704; 1432-0843
• DOI: 10.1007/s00280-005-0059-7

1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and its analogues have been shown to inhibit proliferation of human cancer cells mediated by vitamin D receptor (VDR). The over-expression of 25-hydroxyvitamin D-24-hydroxylase (CYP24A1), an enzyme involved in the metabolism of 1,25(OH)2D3 and its analogues, is associated with poor prognosis of some human cancers. In this study, we employed real-time reverse transcription PCR to examine the expression of VDR and CYP24A1 mRNA in a cohort of human breast, lung, colon and ovary tumor samples. We found that CYP24A1 mRNA was significantly up-regulated in colon, ovary and lung tumors, but down-regulated in breast tumor relative to the analogous normal tissues. As a comparison, VDR mRNA was modestly down-regulated in colon, breast and lung tumors, but highly up-regulated in ovarian tumors. Treatment of two breast cancer cell lines, SW-620 and MCF-7, and one colon cancer cell line, HT-29, by 1,25(OH)2D3 for 48 h profoundly stimulated CYP24A1 mRNA expression (EC50=0.6, 0.8 and 29.5 nM in SW-620, HT-29 and MCF-7, respectively), but did not significantly affect VDR mRNA expression. Growth as assessed by DNA synthesis was modestly arrested by 1,25(OH)2D3 after 72 h of incubation, but was not altered after a 5-day incubation period. These data suggest that the VDR signaling pathway may be compromised via the modulation of CYP24A1 and VDR in human tumors.