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J. Biol. Chem., Vol. 269, Issue 40, 24531-24533, Oct, 1994

Suppression of rat hepatoma cell growth by expression of phosphatidylethanolamine N-methyltransferase-2

Z Cui, M Houweling and DE Vance
Lipid and Lipoprotein Research Group, University of Alberta, Edmonton, Canada.

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.
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