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.
Olsson
Mats
M
Department of Urology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Gustafsson
Ove
O
Skogastierna
Cristine
C
Tolf
Anna
A
Rietz
Barbara Du
BD
Morfin
Robert
R
Rane
Anders
A
Ekström
Lena
L
D000230:Adenocarcinoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D000368:Aged; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D045744:Cell Line, Tumor; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000235:genetics; D000072474:Cytochrome P450 Family 7; D019175:DNA Methylation; D000077209:Decitabine; D004791:Enzyme Inhibitors / Q000494:pharmacology; D047629:Estrogen Receptor beta / Q000096:biosynthesis* / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D013250:Steroid Hydroxylases / Q000096:biosynthesis* / Q000235:genetics
D004791:Enzyme Inhibitors; D047629:Estrogen Receptor beta; D012333:RNA, Messenger; D000077209:Decitabine; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D000072474:Cytochrome P450 Family 7; C499571:CYP7B1 protein, human; D001374:Azacitidine