TY - JOUR
T1 - Overexpression of PEMT2 downregulates the PI3K/Akt signaling pathway in rat hepatoma cells
AU - Zou, Wei
AU - Li, Zhao Yu
AU - Li, Ya Li
AU - Ma, Ke Li
AU - Tsui, Zhao Chun
N1 - Funding Information:
We thank the Natural Science Foundation of China (NSFC) that supported this study (project no. 39670809). We also thank Dr. Dennis Vance for providing the pemt2-cDNA, the PEMT2 antibody, and for his concerns given to this study.
PY - 2002/3/15
Y1 - 2002/3/15
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Cell proliferation
KW - Growth factor
KW - Hepatoma
KW - PI3K/Akt signaling pathway
KW - Phosphatidylethanolamine N-methyltransferase-2
UR - http://www.scopus.com/inward/record.url?scp=0037088228&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037088228&partnerID=8YFLogxK
U2 - 10.1016/S1388-1981(02)00120-8
DO - 10.1016/S1388-1981(02)00120-8
M3 - Article
C2 - 11960751
AN - SCOPUS:0037088228
SN - 1388-1981
VL - 1581
SP - 49
EP - 56
JO - Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
JF - Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
IS - 1-2
ER -