PMID- 19090006
OWN - NLM
STAT- MEDLINE
DCOM- 20090310
LR  - 20211203
IS  - 0008-543X (Print)
IS  - 0008-543X (Linking)
VI  - 115
IP  - 1
DP  - 2009 Jan 1
TI  - Critical and diverse involvement of Akt/mammalian target of rapamycin signaling 
      in human lung carcinomas.
PG  - 107-18
LID - 10.1002/cncr.23996 [doi]
AB  - BACKGROUND: Aberrant signaling cascades emanating from epidermal growth factor 
      receptor (EGFR) are involved in the complex network of oncogenic signaling in 
      lung carcinomas. One representative cascade is the phosphatidylinositol 
      3-kinase/Akt/mammalian target of rapamycin (mTOR) pathway. METHODS: The authors 
      investigated the involvement of mTOR in the pathobiologic profiles of 150 
      specimens of lung carcinoma by immunohistochemistry and immunoblotting in 
      correlation with the upstream and downstream proteins Akt and p70S6-kinase (S6K), 
      respectively. RESULTS: Immunohistochemistry revealed Akt activation in 44% of 
      tumors and mTOR expression in 68.7% of tumors, and the preponderance of 
      activation was observed in adenocarcinoma (AC) (100%). Phosphorylated mTOR 
      (p-mTOR) was observed in 53.3% of tumors and had the highest frequency in AC 
      (89.7%). In AC, the frequency of p-mTOR staining was higher in the well 
      differentiated subtype, in particular, in the acinar structure. However, little 
      correlation was observed between the activation of mTOR and Akt, except in the 5 
      AC specimens that harbored an EGFR gene mutation, which exhibited constitutive 
      activation of both Akt and mTOR. Conversely, in squamous cell carcinomas, mTOR 
      activation was associated with a significantly higher frequency of lymph node 
      metastasis. CONCLUSIONS: The results of this study suggested the dual functions 
      of mTOR. First, mTOR may function not only in the proliferation of tumor cells as 
      an effector molecule downstream of EGFR but also possibly in the morphogenesis of 
      AC. Second, the activation of mTOR may play a key role in metastasis in squamous 
      cell carcinoma. Overall, the current results demonstrated the potential for the 
      application of rapamycin, an mTOR inhibitor, as an additional novel component of 
      chemotherapy for a defined subset of patients with lung carcinoma.
CI  - Copyright (c) 2008 American Cancer Society.
FAU - Dobashi, Yoh
AU  - Dobashi Y
AD  - Department of Pathology and Thoracic Surgery, Saitama Medical Center, Jichi 
      Medical University, Saitama, Japan. ydobashi@omiya.jichi.ac.jp
FAU - Suzuki, Shioto
AU  - Suzuki S
FAU - Matsubara, Hirochika
AU  - Matsubara H
FAU - Kimura, Maiko
AU  - Kimura M
FAU - Endo, Shunsuke
AU  - Endo S
FAU - Ooi, Akishi
AU  - Ooi A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer
JT  - Cancer
JID - 0374236
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Adenocarcinoma/metabolism/pathology
MH  - Humans
MH  - Lung Neoplasms/*metabolism/pathology
MH  - Neoplasm Metastasis
MH  - Neoplasms, Squamous Cell/metabolism/pathology
MH  - Phosphorylation
MH  - Protein Kinases/*metabolism
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Ribosomal Protein S6 Kinases, 70-kDa/metabolism
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases
EDAT- 2008/12/18 09:00
MHDA- 2009/03/11 09:00
CRDT- 2008/12/18 09:00
PHST- 2008/12/18 09:00 [entrez]
PHST- 2008/12/18 09:00 [pubmed]
PHST- 2009/03/11 09:00 [medline]
AID - 10.1002/cncr.23996 [doi]
PST - ppublish
SO  - Cancer. 2009 Jan 1;115(1):107-18. doi: 10.1002/cncr.23996.