Expression of VDR and CYP24A1 mRNA in human tumors.
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.
Anderson
Mark G
MG
Abbott Laboratories, R4CM, AP52, 200 Abbott Park Rd., Abbott Park, IL 60064, USA.
Nakane
Masaki
M
Ruan
Xiaoan
X
Kroeger
Paul E
PE
Wu-Wong
J Ruth
JR
D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D002117:Calcitriol / Q000378:metabolism; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology*; D004247:DNA / Q000096:biosynthesis; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000473:pathology*; D012333:RNA, Messenger / Q000096:biosynthesis; D018167:Receptors, Calcitriol / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013250:Steroid Hydroxylases / Q000096:biosynthesis* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D065668:Vitamin D3 24-Hydroxylase
D012333:RNA, Messenger; D018167:Receptors, Calcitriol; D004247:DNA; D013250:Steroid Hydroxylases; C585549:CYP24A1 protein, human; D065668:Vitamin D3 24-Hydroxylase; D002117:Calcitriol