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Involvement of the Akt/mTOR pathway on EGF‐induced cell transformation
Author(s) -
Nomura Masaaki,
He Zhiwei,
Koyama Ichiko,
Ma WeiYa,
Miyamoto Kenichi,
Dong Zigang
Publication year - 2003
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.10140
Subject(s) - pi3k/akt/mtor pathway , protein kinase b , rptor , p70 s6 kinase 1 , microbiology and biotechnology , biology , phosphorylation , epidermal growth factor , ribosomal protein s6 , cell growth , akt1 , mtorc2 , cancer research , signal transduction , mtorc1 , biochemistry , receptor
Abstract Our previous study demonstrated that phosphatidylinositol 3‐kinase (PI3K) is necessary for epidermal growth factor (EGF)–induced cell transformation in mouse epidermal JB6 cells. Akt and the mammalian target of rapamycin (mTOR) are regarded as PI3K downstream effectors. Therefore, in this study, we investigated the role of Akt and mTOR on EGF‐induced cell transformation in JB6 cells using rapamycin, a specific mTOR inhibitor, and cells expressing dominant negative mutants of Akt1 (DNM‐Akt1). We found that the treatment of cells with rapamycin inhibited EGF‐induced cell transformation but only slightly inhibited JB6 cell proliferation at 72 h. Although LY294002, a PI3K inhibitor, attenuated EGF‐induced activator protein 1 (AP‐1) activation, treatment with rapamycin did not affect AP‐1 activity. Treatment with rapamycin inhibited EGF‐induced phosphorylation and activation of ribosomal p70 S6 protein kinase (p70 S6K), an mTOR downstream target, but had no effect on phosphorylation and activation of Akt. Rapamycin also had no effect on EGF‐induced phosphorylation of extracellular signal–regulated protein kinases (ERKs). We showed that introduction of DNM‐Akt1 into JB6 mouse epidermal Cl 41 (JB6 Cl 41) cells inhibits EGF‐induced cell transformation without blocking cell proliferation. The expression of DNM‐Akt1 also suppressed EGF‐induced p70 S6K activation as well as Akt activation. These results indicated an involvement of the Akt/mTOR pathway in EGF‐induced cell transformation in JB6 cells. © 2003 Wiley‐Liss, Inc.