Induction of v-mos and activated Ha-ras oncogene expression in quiescent NIH 3T3 cells causes intracellular alkalinisation and cell-cycle progression.

We have tested the effect of the expression of the v-mos oncogene, and the activated human Ha-ras oncogene and its proto-oncogene form on the intracellular pH and on cell cycle progression. The Ha-ras proto-oncogene and the oncogenes under the transcriptional control of the MMTV-LTR promoter were introduced into NIH 3T3 cells. The cells were synchronized at G0/G1 in low-serum medium and the transfected genes were induced by glucocorticoid hormone addition to the growth medium. Expression of the v-mos and the activated form of Ha-ras oncogenes mimics the effect of growth factors and activates the Na+/H+ antiporter. The oncogenes increase the internal pH and provoke initiation of S-phase. The proto-oncogene form of Ha-ras does not induce intracellular alkalinisation and has only a weak mitogenic effect. Our results suggest the oncogenic proteins p21ras and p37mos influence the mitogenic signal transduction pathways at a point prior to the activation of the Na+/H+ antiporter.