Cytochrome P450 2B6 is a growth-inhibitory and prognostic factor for prostate cancer
Cytochrome P450 2B6 is a growth-inhibitory and prognostic factor for prostate cancer
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DOI：
10.1002/pros.20597
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发表时间：
2007-07-01
期刊：
影响因子：
2.8
通讯作者：
Inoue, Satoshi
中科院分区：
文献类型：
--
作者：
Kumagai, Jinpei;Fujimura, Tetsuya;Inoue, Satoshi
背景细胞色素P450（CYP）影响致癌物、药物和激素（包括睾酮）的生物效应。其中，细胞色素P450 2136（CYP2B6）在睾酮失活中起着关键作用。在本研究中，我们检测了CYP2136在人前列腺组织和前列腺癌中的表达。对98例良性前列腺组织和106例恶性前列腺组织进行了免疫组化分析，并审查了患者的临床、病理和生存数据。我们还研究了CYP2136在LNCaP（人前列腺癌细胞系）中的稳定表达是否影响细胞增殖。与前列腺癌细胞相比，CYP2136在正常上皮细胞中大量表达。在106个样品中的75个（71%）中，在癌组织样品的细胞质中发现显著的CYP2136免疫染色。CYP2136免疫反应性与高Gleason评分呈负相关（P < 0.001）。CYP2136免疫反应性降低与预后不良显著相关（P < 0.0001）。单变量和多变量风险分析显示，CYP2136表达降低与癌症特异性生存率差显著相关（分别为P = 0.0028和0.0142）。此外，CYP2B6在LNCaP细胞中的过表达显著降低睾酮诱导的增殖。这些结果表明，CYP2B6的表达下降可能在前列腺癌的发生发展中起作用，并可作为人类前列腺癌的预后预测。
BACKGROUND. Cytochrome P450s (CYPs) influence the biological effects of carcinogens, drugs and hormones including testosterones. Among them, Cytochrome P450 2136 (CYP2B6) plays a,critical role in the deactivation of testosterone. In the present study, we examined CYP2136 expression in human prostate tissues and prostate cancer.METHODS. Immunohistochernical 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 CYP2136 in LNCaP (human prostate cancer cell line) influences cellular proliferation.RESULTS. CYP2136 was abundantly expressed in the normal epithelial cells compared to the prostate cancer cells. Significant immunostaining of CYP2136 was found in 75 of 106 samples (71 %), in the cytoplasm of cancerous tissue samples. CYP2136 immunoreactivity was inversely correlated with high Gleason score (P < 0.001). Decreased immunoreactivity of CYP2136 significantly correlated with poor prognosis (P < 0.0001). Univariate and multivariate hazard analyses revealed a significant correlation of decreased CYP2136 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.