SUPPRESSION OF RAT HEPATOMA-CELL GROWTH BY EXPRESSION OF PHOSPHATIDYLETHANOLAMINE N-METHYLTRANSFERASE-2

The expression of rat liver phosphatidylethanolamine N-methyltransfera se-2 (PEMT2) in McA-RH7777 rat hepatoma cells resulted in the unexpect ed inhibition of cell growth. There was a strict correlation (r = 0.97 3) between the level of expression of the enzyme activity and the gene ration time for hepatoma cell division. Expression of other foreign pr oteins via the same vector did not inhibit McA-RH7777 cell growth; thu s, retardation of cell division was specific for the methyltransferase . Addition of 1 mu M 3-deazaadenosine, which causes inhibition of phos phatidylethanolamine methylation, reversed the PEMT2-mediated inhibiti on of cell division. Transfection of a line of Chinese hamster ovary c ells with PEMT2 had no effect on the division of these cells. Inductio n of hepatic tumors in rats with N-nitrosodiethylamine coincided with a striking decrease in methyltransferase activity and immunoreactive p rotein in the tumor nodules. Thus, data from studies in cell culture a nd intact rats suggest a regulatory role for PEMT2 in hepatocyte cell growth and possibly in the development of liver cancer.