title: Expression and clinical significance of mTOR in surgically resected non-small cell lung cancer tissues: a case control study.
abstract: OBJECTIVE
  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.
authors: Department of Oncology, Beijing Chest Hospital, Capital Medical University of China, Beijing, China. liuzhe1968@yahoo.com.cn
authors: Zhe
authors: Z
authors: Liu
authors: Liang
authors: L
authors: Wang
authors: Li-Na
authors: LN
authors: Zhang
authors: Yue
authors: Y
authors: Wang
authors: Wen-Tao
authors: WT
authors: Yue
authors: Qi
authors: Q
authors: Li
mesh_terms: D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung; D016022:Case-Control Studies; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D017526:Receptor, IGF Type 1