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Expression and Clinical Significance of mTOR in Surgically Resected Non-small Cell Lung Cancer Tissues: a Case Control Study

  • Liu, Zhe (Department of Oncology, Beijing Chest Hospital, Capital Medical University of China) ;
  • Wang, Liang (Department of Molecular Biology Laboratory, Beijing Chest Hospital, Capital Medical University of China) ;
  • Zhang, Li-Na (Department of Molecular Biology Laboratory, Beijing Chest Hospital, Capital Medical University of China) ;
  • Wang, Yue (Department of Molecular Biology Laboratory, Beijing Chest Hospital, Capital Medical University of China) ;
  • Yue, Wen-Tao (Department of Molecular Biology Laboratory, Beijing Chest Hospital, Capital Medical University of China) ;
  • Li, Qi (Department of Oncology, Beijing Chest Hospital, Capital Medical University of China)
  • Published : 2012.12.31

Abstract

Aims: Mammalian target of rapamycin (mTOR) is master regulator of the PI3K/Akt/mTOR pathway and plays an important role in NSCLCs. Here we characterized mRNA and protein expression levels of mTOR and its functional associated molecules including PTEN, IGF-1R and 4EBP1 in surgically resected NSCLCs. Methods: Fifty-four patients with NSCLCs who underwent pulmonary resection were included in current study. mRNA levels of mTOR, PTEN, IGF-1R, and 4EBP1 were evaluated by RT-PCR and protein expression of mTOR, PTEN, and IGF-1R by immunohistochemistry (IHC). Association of expression of the relevant molecules with clinical characteristics, as well as correlations between mTOR and PTEN, 4EBP1 and IGF-1R were also assessed. Results: The results of RT-PCR showed that in NSCLCs, the expression level of mTOR increased, while PTEN, 4EBP1 and IGF-1R decreased. Statistical analysis indicated high IGF-1R expression was correlated with advanced clinical stage (stage III) and PTEN expression was reversely associated with tumor size (P=0.16). The results of IHC showed mTOR positive staining in 51.8% of cases, while IGF-1R positive staining was found in 83.3% and loss of PTEN in 46.3%. Protein expression of mTOR was correlated with its regulators, PTEN and IGF-1R, to some extent. Conclusions: Abnormal activation of mTOR signaling, high expression of IGF-1R, and loss of PTEN were observed in resected NSCLC specimens. The poor expression agreement of mTOR with its regulators, PTEN, and IGF-1R, implied that combination strategy of mTOR inhibitors with other targets hold significant potential for NSCLC treatment.

Keywords

NSCLC;mTOR;PTEN;IGF;1R;4EBP1

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