LEUKEMIA INHIBITORY FACTOR INDUCES MITOGENESIS IN SWISS 3T3 CELLS ANDSELECTIVE ENHANCEMENT VIA A VARIETY OF SIGNALING EVENTS

Leukaemia inhibitory factor (LIF) stimulates cellular DNA synthesis in confluent quiescent Swiss 3T3 cells. Insulin and prostaglandin E-1 (P GE(1)), which fail tea stimulate DNA synthesis alone, potentiate this effect. Prostaglandin F-2 alpha (PGF(2 alpha)), which is mitogenic in these cells, enhances the effect of LIF on DNA synthesis. TGF beta(1) increases the effect of PGF(2 alpha) but not that of LIF, R-59022, a d iacylglycerol kinase inhibitor which increases protein kinase C (PKC) activity, enhances only the PGF(2 alpha) response. 13-Tetradecanoyl-12 -phorbolacetate-mediated PKC depletion prevents the action of PGF(2 al pha) but not that of LIF, nor the PGF(2 alpha) potentiation of LIF-sti mulated DNA synthesis. 1-Oleoyl-2-acetylglycerol, a PKC and tyrosine k inase (TK) activator which mimics some of the PGF(2 alpha), effects, e nhances only LIF-induced DNA synthesis in cells possessing intact PKC activity. These results suggest that stimulation of DNA synthesis by L IF, as well as its enhancement by PGF(2 alpha), may occur via a signal ling pathway independent of PKC activation. (C) 1997 Academic Press.