Clinical significance of steroid and xenobiotic receptor and its targeted gene CYP3A4 in human prostate cancer

被引：30

作者：

Fujimura, Tetsuya ^{[1
]}

Takahashi, Satoru ^{[2
]}

Urano, Tomohiko ^{[3
,4
]}

Tanaka, Toshiya ^{[5
]}

Zhang, Weiguang ^{[4
]}

Azuma, Kotaro ^{[3
,4
]}

Takayama, Kenich ^{[3
,4
]}

Obinata, Daisuke ^{[2
]}

Murata, Taro ^{[1
]}

Horie-Inoue, Kuniko ^{[6
]}

Kodama, Tatsuhiko ^{[5
]}

Ouchi, Yasuyoshi ^{[3
]}

Homma, Yukio ^{[1
]}

Inoue, Satoshi ^{[3
,4
]}

机构：

[1] Univ Tokyo, Grad Sch Med, Dept Urol, Tokyo, Japan

[2] Nihon Univ, Grad Sch Med, Dept Urol, Tokyo, Japan

[3] Univ Tokyo, Dept Geriatr Med, Tokyo, Japan

[4] Univ Tokyo, Grad Sch Med, Dept Antiaging Med, Tokyo, Japan

[5] Univ Tokyo, Res Ctr Adv Sci & Technol, Tokyo, Japan

[6] Res Ctr Genom Med, Div Gene Regulat & Signal Transduct, Saitama, Japan

来源：

CANCER SCIENCE | 2012年 / 103卷 / 02期

基金：

日本学术振兴会;

关键词：

ANDROGEN-DEPRIVATION THERAPY; RAT VENTRAL PROSTATE; CYTOCHROME-P450; 3A4; EXPRESSION; SXR; IDENTIFICATION; PROLIFERATION; GROWTH;

D O I：

10.1111/j.1349-7006.2011.02143.x

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The steroid and xenobiotic receptor (SXR) regulates cytochrome P450 (CYP) enzymes, which are key inactivators of testosterone in the liver and prostate. In the present study, we investigated SXR expression in human prostate tissues. We determined SXR immunoreactivity using an anti-SXR antibody in benign (n = 78) and cancerous (n = 106) tissues obtained by radical prostatectomy. Stained slides were evaluated for the proportion and staining intensity of immunoreactive cells. Total immunoreactivity (IR) scores (range: 08) were calculated as the sum of the proportion and intensity scores. Associations between the clinicopathological features of the patients, SXR status, and CYP3A4 immunoreactivity were analyzed. Western blot analyses validated the specificity of the anti-SXR antibody in 293T cells transfected with pcDNAFLAGSXR. Positive (IR score: = 2) nuclear SXR staining was observed in 91% (71/78) of benign foci and 47% (50/106) of cancerous lesions. Immunoreactivity scores were significantly lower in the cancerous lesions than in the benign foci (P < 0.0001). Clinicopathological analyses showed that cancer-specific survival in patients with high SXR IR scores (=4) was significantly increased (P = 0.046). Combined data of present and previous studies showed that high IR scores for both the SXR and CYP3A4 correlated with significantly better cancer-specific survival rates in multivariate regression analyses (hazard ratio: 2.15, 95% confidence interval: 1.253.55, P = 0.007). We showed differential SXR expression in human prostate tissues. The high expression of the SXR and CYP3A4 is a strong prognostic indicator of favorable outcomes in prostate cancer, and could be a therapeutic target. (Cancer Sci 2012; 103: 176180)

引用

页码：176 / 180

页数：5

共 24 条

[1] ASSOCIATION OF P53 PROTEIN EXPRESSION WITH TUMOR-CELL PROLIFERATION RATE AND CLINICAL OUTCOME IN NODE-NEGATIVE BREAST-CANCER [J].