Regulation and expression of human CYP7B1 in prostate: overexpression of CYP7B1 during progression of prostatic adenocarcinoma.

BACKGROUND: Cytochrome P450 (CYP) 7B1 is involved in many metabolic processes including androgen metabolism. Cytochrome P450 (CYP) 7B1 is expressed within the prostate and may determine the levels of the natural estrogen receptor beta (ERbeta) ligand 5alpha-androstane-3beta,17beta-diol (3betaAdiol) available and hence affect the regulation of prostate proliferation. We hypothesized that CYP7B1 expression is increased in prostate tumors and that promoter methylation contributes to the regulation of CYP7B1 expression in human prostate tissue.
METHODS: Expression of the CYP7B1 gene and protein in clinical prostate tissues and prostate cancer cell lines were investigated using real-time PCR and immunohistochemistry. The methylation status of the CYP7B1 gene was analyzed using methylation-specific PCR (MSP).
RESULTS: The immunohistochemical results demonstrate that high expression of CYP7B1 protein occurs in high-grade prostatic intraepithelial neoplasia (PIN) and adenocarcinomas. The ERbeta/CYP7B1 mRNA ratio was significantly lower in tumor compared to the non-tumor area. The MSP analysis indicate that local methylation of CYP7B1 promoter region is an important mechanism involved in down-regulation of CYP7B1 in human prostate tissue.
CONCLUSIONS: This is the first report showing that CYP7B1 is overexpressed in high-grade PIN and in prostate cancer and that local methylation of CYP7B1 promoter region may have significant effect on gene transcription. 2007 Wiley-Liss, Inc