THE COMPETENCE PROGRESSION MODEL IN CHO-K1 CELLS - THE RELATIONSHIP BETWEEN PROTEIN-KINASE-C AND IMMEDIATE-EARLY GENE-EXPRESSION IN THE INSULIN MITOGENIC SIGNAL

CHO-K1 cells grow in a defined medium with insulin, at physiological c oncentrations, as the only hormone. IGF-I can substitute for insulin. Quiescent cells require a 9-10-h lag, subsequent to the addition of in sulin, to synthesize DNA. The phorbol ester, 12-0-tetradeconoylphorbol 13-acetate (TPA), cannot support growth of these cells, is a more eff ective inducer than insulin of c-fos, c-myc, c-jun, jun-B, Krox-20, Kr ox 24, fra-1 and JE, and induces fra-1, JE and c-myc with different ki netics from those of insulin. The addition of insulin + TPA to quiesce nt cells produces a synergistic effect on DNA synthesis but not on the expression of immediate early genes. Pretreatment of these cells with TPA or insulin decreases the required lag time for DNA synthesis by 3 h in a protein-synthesis-independent manner. These results, together with other experiments, demonstrate that [1] the insulin signal is ind ependent of PKC, [2] insulin acts as a weak competence and a strong pr ogression factor, while TPA behaves as a strong competence factor, and [3] the 9-10-h lag is made up of a 3-h period which is independent of protein synthesis, advancing the cells to a post-G(o) state of 'compe tence'.