Prognostic and therapeutic implications of mTORC1 and Rictor expression in human breast cancer
Prognostic and therapeutic implications of mTORC1 and Rictor expression in human breast cancer
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DOI：
10.3892/or.2013.2346
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发表时间：
2013-05-01
期刊：
影响因子：
4.2
通讯作者：
Mokbel, K.
中科院分区：
文献类型：
--
作者：
Wazir, U.;Newbold, R. F.;Mokbel, K.
哺乳动物雷帕霉素靶蛋白（mTOR）在调节细胞代谢、生长和增殖方面发挥着关键作用。它形成两种多蛋白质复合物，称为复合物1（mTORC 1）和2（mTORC 2）。Raptor和Rictor分别是mTORC 1和mTORC 2的核心蛋白。本研究旨在探讨mTORC 1、Rictor和Raptor mRNA表达与人乳腺癌的关系。此外，mTORC1和hTERT之间的相关性进行了研究。使用逆转录和定量PCR分析乳腺癌组织（n=150）和正常组织（n=31）。转录水平与临床病理数据相关。在乳腺癌组织（P=0.0018）、高级别肿瘤（2级vs.3级，P=0.047）、导管肿瘤（P=0.0014）中观察到较高的mTOR表达，并且与较差的总生存率相关（P=0.01）。背景乳腺组织中Rictor表达显著高于肿瘤组织，与诺丁汉预后指数（NPI 1 vs. 2，P=0.03）和肿瘤分级（1级vs. 3，P=0.01）呈负相关，与更好的总体（P=0.037）和无病生存期（P=0.048）相关。Raptor mRNA在肿瘤组织中的表达高于正常组织。此外，Raptor的表达与较高的肿瘤分级相关（1级与3级，P=0.027）。mTOR与hTERT呈显著正相关（P
The mammalian target of rapamycin (mTOR) plays a key role in the regulation of cellular metabolism, growth and proliferation. It forms two multi-protein complexes known as complex 1 (mTORC1) and 2 (mTORC2). Raptor and Rictor are the core proteins for mTORC1 and mTORC2, respectively. This study examines the relationship between mTORC1, Rictor and Raptor mRNA expression and human breast cancer. Furthermore, the correlation between mTORC1 and hTERT was investigated. Breast cancer tissues (n=150) and normal tissues (n=31) were analysed using reverse transcription and quantitative PCR. Transcript levels were correlated with clinicopathological data. Higher mTOR expression was noted in breast cancer tissue (P=0.0018), higher grade tumours (grade 2 vs. 3, P=0.047), in ductal tumours (P=0.0014), and was associated with worse overall survival (P=0.01). Rictor expression was significantly higher in background breast tissues compared with tumours and was inversely related to the Nottingham Prognostic Index (NPI1 vs. 2, P=0.03) and tumour grade (grade 1 vs. 3, P=0.01) and was associated with better overall (P=0.037) and disease-free survival (P=0.048). The mRNA expression of Raptor was higher in tumours compared with normal tissues. Furthermore, the expression of Raptor was associated with a higher tumour grade (grade 1 vs. 3, P=0.027). A highly significant positive correlation between mTOR and hTERT (P