Overexpression of PEMT2 downregulates the PI3K/Akt signaling pathway in rat hepatoma cells

Wei Zou, Zhaoyu Li, Ya Li Li, Ke Li Ma, Zhao Chun Tsui

Research output: Contribution to journalArticle

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Abstract

Phosphatidylethanolamine N-methyltransferase 2 (PEMT2) is an isoform of PEMT that converts phosphatidylethanolamine to phosphatidylcholine in mammalian liver. Overexpression of PEMT2 led to inhibition of proliferation of hepatoma cells [J. Biol. Chem. 269 (1994) 24531]. The present study aims to unravel the molecular mechanism of the reduced proliferation, especially the signaling transducer proteins involved in this process. Thus, we chose PI3K/Akt pathway that is initiated by growth factors and leads to cell survival and proliferation. Rat hepatoma CBRH-7919 cells transfected with pemt2-cDNA showed that: (1) signaling proteins including c-Met, PDGF receptor, PI3K, Akt and Bcl-2 all had reduced expression as shown by Western blotting studies; (2) flow cytometric and DNA ladder assays showed that 22.9% of the pemt2-transfected cells were undergoing apoptosis; (3) the activity of Akt was decreased as shown by Western blotting using antibody directed against p-Akt (Thr308); (4) wortmannin and PD98059, inhibitors of PI3K and MEK, respectively, both inhibited Akt activity, indicating that PI3K and MAPK pathways were merging at Akt in CBRH-7919 cells. The above results suggest that overexpression of PEMT2 strongly downregulated the PI3K/Akt signaling pathway at multiple sites and induced apoptosis. This, at least partly, explains the molecular mechanism of impaired proliferation induced by pemt2 transfection.

Original languageEnglish (US)
Pages (from-to)49-56
Number of pages8
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Volume1581
Issue number1-2
DOIs
StatePublished - Mar 15 2002
Externally publishedYes

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Keywords

  • Apoptosis
  • Cell proliferation
  • Growth factor
  • Hepatoma
  • Phosphatidylethanolamine N-methyltransferase-2
  • PI3K/Akt signaling pathway

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Biophysics

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