Suppression of rat hepatoma cell growth by expression of phosphatidylethanolamine N-methyltransferase-2.
The expression of rat liver phosphatidylethanolamine N-methyltransferase-2 (PEMT2) in McA-RH7777 rat hepatoma cells resulted in the unexpected inhibition of cell growth. There was a strict correlation (r = 0.973) between the level of expression of the enzyme activity and the generation time for hepatoma cell division. Expression of other foreign proteins via the same vector did not inhibit McA-RH7777 cell growth; thus, retardation of cell division was specific for the methyltransferase. Addition of 1 microM 3-deazaadenosine, which causes inhibition of phosphatidylethanolamine methylation, reversed the PEMT2-mediated inhibition of cell division. Transfection of a line of Chinese hamster ovary cells with PEMT2 had no effect on the division of these cells. Induction of hepatic tumors in rats with N-nitrosodiethylamine coincided with a striking decrease in methyltransferase activity and immunoreactive protein in the tumor nodules. Thus, data from studies in cell culture and intact rats suggest a regulatory role for PEMT2 in hepatocyte cell growth and possibly in the development of liver cancer.
Cui
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Lipid and Lipoprotein Research Group, University of Alberta, Edmonton, Canada.
Houweling
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Vance
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D000818:Animals; D002455:Cell Division; D008099:Liver / Q000201:enzymology; D008114:Liver Neoplasms, Experimental / Q000201:enzymology / Q000473:pathology*; D008780:Methyltransferases / Q000502:physiology*; D010713:Phosphatidylcholines / Q000096:biosynthesis; D050918:Phosphatidylethanolamine N-Methyltransferase; D010714:Phosphatidylethanolamines / Q000378:metabolism; D051381:Rats; D014372:Tubercidin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; C018258:3-deazaadenosine; D008780:Methyltransferases; D050918:Phosphatidylethanolamine N-Methyltransferase; D014372:Tubercidin