Effect of retinoic acid and phorbol-12-myristate-13-acetate on glycosyltransferase activities in normal and transformed cells.

Retinoic acid was found to increase the activity of cytidine monophosphosialic acid:lactosylceramide sialyltransferase activity in a nontransformed clonal hamster cell line, NIL 8, and a virally transformed clone, NIL 8-HSV. The potent tumor promoter phorbol-12-myristate-13-acetate (PMA) had no significant effect on sialyltransferase activity in NIL 8 cells but stimulated this activity almost 6-fold when added to NIL 8-HSV cells. There was a synergistically additive effect on sialyltransferase activity when PMA was added to NIL 8 cells in concert with retinoic acid. On the other hand neither PMA nor retinoic acid had an appreciable effect on two other glycosyltransferases measured, uridine diphospho-N-acetylgalactosamine:globotriaosylceramide N-acetylgalactosaminyl-transferase and uridine diphosphogalactose:asialoagalactofetuin galactosyltransferase. Examination of sialyltransferase activity in a human epidermoid carcinoma cell line showed a large increase in enzyme activity in response to retinoic acid administration. Two nontransformed hamster cell lines had less basal sialyltransferase activity but also showed marked elevations after retinoic acid treatment. It is proposed that one of the molecular mechanisms underlying the biological effects of retinoic acid and PMA may be an increase in sialyltransferase activity. Possible regulatory mechanisms are discussed.