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Cytochrome P450 2B6 is a growth‐inhibitory and prognostic factor for prostate cancer
Author(s) -
Kumagai Jinpei,
Fujimura Tetsuya,
Takahashi Satoru,
Urano Tomohiko,
Ogushi Tetsuo,
HorieInoue Kuniko,
Ouchi Yasuyoshi,
Kitamura Tadaichi,
Muramatsu Masami,
Blumberg Bruce,
Inoue Satoshi
Publication year - 2007
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20597
Subject(s) - lncap , prostate cancer , prostate , medicine , immunostaining , cyp2b6 , immunohistochemistry , cancer , cancer research , oncology , endocrinology , cytochrome p450 , cyp1a2 , metabolism
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. Prostate 67: 1029–1037, 2007. © 2007 Wiley‐Liss, Inc.