Activation of the mammalian target of rapamycin signalling pathway in prostate cancer and its association with patient clinicopathological characteristics
Activation of the mammalian target of rapamycin signalling pathway in prostate cancer and its association with patient clinicopathological characteristics
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前列腺癌中雷帕霉素信号通路哺乳动物靶点的激活及其与患者临床病理特征的关系
DOI：
10.1111/j.1464-410x.2009.08538.x
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发表时间：
2009-10-01
影响因子：
4.5
通讯作者：
Yao, Xu Dong
中科院分区：
文献类型：
--
作者：
Dai, Bo;Kong, Yun Yi;Yao, Xu Dong
目的探讨雷帕霉素靶蛋白（mTOR）信号通路在中国前列腺癌患者中的激活水平，因为该通路在许多人类癌症中被过度激活，是癌症治疗的一个有吸引力的靶点。在来自182名前列腺癌患者、20名良性前列腺增生（BPH）患者和10名高级别前列腺上皮内瘤变（HGPIN）患者的组织中。p-Akt、p-mTOR、p-4 E-BP 1和p-p70 S6 K在前列腺癌组织中的表达水平显著高于BPH和HGPIN组织。在182例前列腺癌患者中，p-mTOR的表达水平与其上游p-Akt及下游p-4 E-BP 1和p-p70 S6 K的表达水平呈显著正相关。肿瘤Gleason评分与p-Akt和p-mTOR表达水平显著相关，而与p-4 E-BP 1和p-p70 S6 K表达水平无关。然而，p-4 E-BP 1和p-p70 S6 K表达水平在原发癌病变与患者的T分期和远处转移有统计学意义相关。mTOR通路的激活可能参与前列腺癌的发生和发展。mTOR通路的激活与患者临床病理变量之间的关联表明，并非所有患者都同样适合靶向mTOR通路的治疗策略。
OBJECTIVETo evaluate the activation level of the mammalian target of rapamycin (mTOR) signalling pathway in Chinese patients with prostate cancer, as this pathway is over-activated in many human cancers and is an attractive target for cancer therapy.PATIENTS AND METHODSWe used immunohistochemistry to investigate the activation level of five important markers of the mTOR pathway, including PTEN, p-Akt, p-mTOR, p-p70S6K and p-4E-BP1, in tissues from 182 patients with prostate cancer, 20 with benign prostatic hyperplasia (BPH) and 10 with high-grade prostatic intraepithelial neoplasia (HGPIN). The expression levels of these five markers were associated with patient clinical and pathological characteristics.RESULTSExpression levels of p-Akt, p-mTOR, p-4E-BP1 and p-p70S6K were significantly higher in prostate cancer tissues than in BPH and HGPIN tissues. In 182 patients with prostate cancer the p-mTOR expression level significantly and positively correlated with its upstream p-Akt and downstream p-4E-BP1 and p-p70S6K expression levels. The cancer Gleason score was significantly correlated with p-Akt and p-mTOR expression level but not with p-4E-BP1 and p-p70S6K expression level. However, the p-4E-BP1and p-p70S6K expression levels in primary cancer lesions were statistically significantly correlated with patient T stage and distant metastases.CONCLUSIONSMost patients with prostate cancer have at least one component of the mTOR signalling pathway activated. The activation of the mTOR pathway might be involved in prostate cancer development and progression. The association between activation of mTOR pathway and patient clinicopathological variables suggested that not all patients are equally amenable to treatment strategies targeting the mTOR pathway.