Cytochrome P450 2B6 is a growth-inhibitory and prognostic factor for prostate cancer.
BACKGROUND
Cytochrome P450s (CYPs) influence the biological effects of carcinogens, drugs and hormones including testosterones. Among them, Cytochrome P450 2B6 (CYP2B6) plays a critical role in the deactivation of testosterone. In the present study, we examined CYP2B6 expression in human prostate tissues and prostate cancer.


METHODS
Immunohistochemical analysis was performed in 98 benign and 106 malignant prostate tissues and patients' charts were reviewed for clinical, pathologic and survival data. We also investigated whether stable expression of CYP2B6 in LNCaP (human prostate cancer cell line) influences cellular proliferation.


RESULTS
CYP2B6 was abundantly expressed in the normal epithelial cells compared to the prostate cancer cells. Significant immunostaining of CYP2B6 was found in 75 of 106 samples (71%), in the cytoplasm of cancerous tissue samples. CYP2B6 immunoreactivity was inversely correlated with high Gleason score (P < 0.001). Decreased immunoreactivity of CYP2B6 significantly correlated with poor prognosis (P < 0.0001). Univariate and multivariate hazard analyses revealed a significant correlation of decreased CYP2B6 expression with poor cancer-specific survival (P = 0.0028 and 0.0142, respectively). Furthermore, overexpression of CYP2B6 in LNCaP cells significantly decreased testosterone-induced proliferation.


CONCLUSIONS
These results demonstrated that decreased expression of CYP2B6 might play a role in the development of prostate cancer, and be useful as the prognostic predictor for human prostate cancer.
Kumagai
Jinpei
J
Department of Urology, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo, Japan.
Fujimura
Tetsuya
T
Takahashi
Satoru
S
Urano
Tomohiko
T
Ogushi
Tetsuo
T
Horie-Inoue
Kuniko
K
Ouchi
Yasuyoshi
Y
Kitamura
Tadaichi
T
Muramatsu
Masami
M
Blumberg
Bruce
B
Inoue
Satoshi
S
D000368:Aged; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism*; D019556:COS Cells; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002522:Chlorocebus aethiops; D065702:Cytochrome P-450 CYP2B6; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D011467:Prostate / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D013739:Testosterone / Q000494:pharmacology; D014162:Transfection
D013739:Testosterone; D001189:Aryl Hydrocarbon Hydroxylases; C585599:CYP2B6 protein, human; D065702:Cytochrome P-450 CYP2B6; D010089:Oxidoreductases, N-Demethylating