PMID- 20008839
OWN - NLM
STAT- MEDLINE
DCOM- 20100416
LR  - 20220331
IS  - 1557-3265 (Electronic)
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 16
IP  - 1
DP  - 2010 Jan 1
TI  - Overexpression of phospho-eIF4E is associated with survival through AKT pathway 
      in non-small cell lung cancer.
PG  - 240-8
LID - 10.1158/1078-0432.CCR-09-0986 [doi]
AB  - PURPOSE: The eukaryotic translation initiation factor complex 4E (eIF4E) is 
      downstream in the mammalian target of rapamycin (mTOR) pathway. This study 
      explored expression of eIF4E and its relationship with the PTEN/AKT and 
      RAS/MEK/ERK pathways in non-small cell lung carcinoma (NSCLC). EXPERIMENTAL 
      DESIGN: The status of phosphorylated eIF4E (p-eIF4E), phosphorylated AKT (p-AKT), 
      PTEN, phosphorylated tuberin (p-TSC2), phosphorylated mTOR (p-mTOR), 
      phosphorylated S6 (p-S6), and phosphorylated Erk1/2 (p-Erk1/2) was studied using 
      immunohistochemical analysis applied to a tissue microarray containing 300 
      NSCLCs. Staining results for each antibody were compared with clinical and 
      pathologic features, and the relationship between staining results was explored. 
      RESULTS: Overexpression of p-eIF4E, p-AKT, p-TSC2, p-mTOR, p-S6, and p-Erk1/2 in 
      NSCLC was found in 39.9%, 78.8%, 5.1%, 46.7%, 27.1%, and 16.6% of tumors, 
      respectively. The phenotype of p-eIF4E correlated positively with that of p-AKT, 
      p-TSC2, and p-S6 (P < 0.001). Overall survival in NSCLC patients was 
      significantly shorter in cases with overexpression of p-eIF4E and p-AKT alone and 
      in combination (log-rank P < 0.001, each). Cases with underexpression of PTEN 
      were limited (6.4%), and this phenotype did not correlate with any clinical 
      variable. In cluster analysis, the p-AKT/p-mTOR/p-eIF4E/p-S6-positive group had 
      significantly shorter survival compared with the survival of all cases (P < 
      0.001). Multivariate analysis showed that p-eIF4E overexpression is an 
      independent prognostic factor for NSCLC (P = 0.004). CONCLUSIONS: This study 
      shows that p-eIF4E expression in addition to p-AKT predicts poor prognosis in 
      NSCLC. Moreover, the correlation between expression of p-eIF4E with p-AKT, as 
      well as p-TSC2 and p-S6, indicates that eIF4E activation through the AKT pathway 
      plays an important role in the progression of NSCLC.
FAU - Yoshizawa, Akihiko
AU  - Yoshizawa A
AD  - Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New 
      York 10065, USA.
FAU - Fukuoka, Junya
AU  - Fukuoka J
FAU - Shimizu, Shigeki
AU  - Shimizu S
FAU - Shilo, Konstantin
AU  - Shilo K
FAU - Franks, Teri J
AU  - Franks TJ
FAU - Hewitt, Stephen M
AU  - Hewitt SM
FAU - Fujii, Takeshi
AU  - Fujii T
FAU - Cordon-Cardo, Carlos
AU  - Cordon-Cardo C
FAU - Jen, Jin
AU  - Jen J
FAU - Travis, William D
AU  - Travis WD
LA  - eng
GR  - ZIC BC011257/ImNIH/Intramural NIH HHS/United States
PT  - Journal Article
DEP - 20091215
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (Eukaryotic Initiation Factor-4E)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - EC 3.1.3.67 (PTEN Phosphohydrolase)
RN  - EC 3.1.3.67 (PTEN protein, human)
SB  - IM
MH  - Carcinoma, Non-Small-Cell Lung/*metabolism/mortality
MH  - Eukaryotic Initiation Factor-4E/*metabolism
MH  - Female
MH  - Humans
MH  - Lung Neoplasms/*metabolism/mortality
MH  - Male
MH  - Mitogen-Activated Protein Kinase 3/metabolism
MH  - PTEN Phosphohydrolase/metabolism
MH  - Phosphorylation
MH  - Prognosis
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Signal Transduction
MH  - Tissue Array Analysis
PMC - PMC7581274
MID - NIHMS1634315
COIS- Disclosure of Potential Conflicts of Interest No potential conflicts of interest 
      were disclosed.
EDAT- 2009/12/17 06:00
MHDA- 2010/04/17 06:00
PMCR- 2020/10/22
CRDT- 2009/12/17 06:00
PHST- 2009/12/17 06:00 [entrez]
PHST- 2009/12/17 06:00 [pubmed]
PHST- 2010/04/17 06:00 [medline]
PHST- 2020/10/22 00:00 [pmc-release]
AID - 1078-0432.CCR-09-0986 [pii]
AID - 10.1158/1078-0432.CCR-09-0986 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2010 Jan 1;16(1):240-8. doi: 10.1158/1078-0432.CCR-09-0986. Epub 
      2009 Dec 15.