The London Breast Institute, Princess Grace Hospital, London, UK.
Oncol Rep. 2013 May;29(5):1969-74. doi: 10.3892/or.2013.2346. Epub 2013 Mar 13.
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<0.00001) was observed. These observations are consistent with the role of mTORC1 in the anti-apoptosis pathway and suggest that selective inhibitors of mTORC1 may be more efficacious in human breast cancer. Our findings support the hypothesis that mTORC1 is an important upregulator of telomerase in breast cancer.
哺乳动物雷帕霉素靶蛋白（mTOR）在细胞代谢、生长和增殖的调节中发挥关键作用。它形成两个多蛋白复合物，分别称为复合物 1（mTORC1）和 2（mTORC2）。Raptor 和 Rictor 分别是 mTORC1 和 mTORC2 的核心蛋白。本研究探讨了 mTORC1、Rictor 和 Raptor mRNA 表达与人类乳腺癌之间的关系。此外，还研究了 mTORC1 与 hTERT 之间的相关性。使用逆转录和定量 PCR 分析了 150 例乳腺癌组织和 31 例正常组织。将转录本水平与临床病理数据相关联。在乳腺癌组织中观察到更高的 mTOR 表达（P=0.0018），高级别肿瘤（2 级与 3 级，P=0.047），导管性肿瘤（P=0.0014），与总体生存较差相关（P=0.01）。Rictor 的表达在背景乳腺组织中明显高于肿瘤组织，并且与诺丁汉预后指数（NPI1 与 2，P=0.03）和肿瘤分级（1 级与 3 级，P=0.01）呈负相关，并且与更好的总生存（P=0.037）和无病生存（P=0.048）相关。Raptor 的 mRNA 表达在肿瘤中高于正常组织。此外，Raptor 的表达与更高的肿瘤分级相关（1 级与 3 级，P=0.027）。观察到 mTOR 和 hTERT 之间高度显著的正相关（P<0.00001）。这些观察结果与 mTORC1 在抗凋亡途径中的作用一致，并表明 mTORC1 的选择性抑制剂可能在人类乳腺癌中更有效。我们的研究结果支持 mTORC1 是乳腺癌中端粒酶的重要上调因子的假说。
