The Mammalian Target of Rapamycin Pathway Is Widely Activated Without PTEN Deletion in Renal Cell Carcinoma Metastases
The Mammalian Target of Rapamycin Pathway Is Widely Activated Without PTEN Deletion in Renal Cell Carcinoma Metastases
复制标题
DOI：
10.1002/cncr.25402
复制
发表时间：
2011-01-15
期刊：
影响因子：
6.2
通讯作者：
Sircar, Kanishka
中科院分区：
文献类型：
--
作者：
Abou Youssif, Tamer;Fahmy, Mona Alam;Sircar, Kanishka
背景：哺乳动物雷帕霉素靶蛋白（mTOR）抑制剂是治疗转移性肾细胞癌（RCC）的一种有前景的药物。由于合理的治疗策略需要了解靶向疾病所需阶段的潜在信号通路的激活状态，因此作者检查了RCC转移灶和匹配的原发性肿瘤中mTOR通路不同组分的激活状态。方法：作者用抗磷脂酰肌醇3 '-激酶、PTEN、磷酸化Akt、磷酸化mTOR和p70 S6的抗体对来自132名患者的转移性RCC样本和25个匹配的原发性RCC子集进行免疫染色。通过荧光原位杂交评估PTEN基因组状态。标志物表达与临床病理变量和生存率相关。研究结果：mTOR信号通路在不同部位的肾细胞癌转移灶中表现出广泛的激活，该信号通路的不同组分之间存在强相关性（P
BACKGROUND: Inhibitors of the mammalian target of rapamycin (mTOR) are emerging as promising therapies for metastatic renal cell carcinoma (RCC). Because rational treatment strategies require understanding the activation status of the underlying signaling pathway being targeted at the desired stage of disease, the authors examined the activation status of different components of the mTOR pathway in RCC metastases and matched primary tumors. METHODS: The authors immunostained metastatic RCC samples from 132 patients and a subset of 25 matched primary RCCs with antibodies against phosphatidylinositol 3'-kinase, PTEN, phospho-Akt, phospho-mTOR, and p70S6. PTEN genomic status was assessed by fluorescent in situ hybridization. Marker expression was correlated to clinicopathologic variables and to survival. RESULTS: The mTOR pathway showed widespread activation in RCC metastases of various sites with strong correlation between different components of this signaling cascade (P