Involvement of the Akt/mTOR pathway on EGF-induced cell transformation

Masaaki Nomura, Zhiwei He, Ichiko Koyama, Wei-Ya Ma, Ken Ichi Miyamoto, Zigang Dong

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

Our previous study demonstrated that phosphatidylinositol 3-kinase (P13K) 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 P13K 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 P13K 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.

Original languageEnglish (US)
Pages (from-to)25-32
Number of pages8
JournalMolecular Carcinogenesis
Volume38
Issue number1
DOIs
StatePublished - Sep 1 2003

Keywords

  • Akt
  • Cell transformation
  • EGF
  • Rapamycin
  • mTOR
  • p70 S6K

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    Nomura, M., He, Z., Koyama, I., Ma, W-Y., Miyamoto, K. I., & Dong, Z. (2003). Involvement of the Akt/mTOR pathway on EGF-induced cell transformation. Molecular Carcinogenesis, 38(1), 25-32. https://doi.org/10.1002/mc.10140