Taub R, Roy A, Dieter R, Koontz J
J Biol Chem. 1987 Aug 5;262(22):10893-7.
In a subline of Reuber H35 rat hepatoma cells that becomes quiescent under serum-deprived conditions, insulin acts as a growth factor. When added to serum-deprived H35 cells, physiologic concentrations of insulin stimulate DNA synthesis, demonstrating that insulin alone is capable of inducing a transition from G0/G1 into S phase. This response, which is induced by nanomolar concentrations of insulin, is mediated directly through the insulin receptor. Here we show that coincident with this growth response, insulin or serum induces dramatic increases in the steady-state levels of c-fos and c-myc mRNAs in serum-deprived H35 cells in a time course similar to that observed in the regenerating liver. Other growth factors, including epidermal growth factor, appear not to affect these cells either in terms of DNA synthesis or c-myc mRNA induction. The phorbol ester phorbol 12-myristate 13-acetate (PMA) also induces c-myc and c-fos mRNAs without inducing DNA synthesis. However, the mechanism of this induction appears to be different from the insulin-induced induction since pretreatment of cells with PMA blocks only the PMA-mediated, not the insulin-mediated, induction of c-myc and c-fos.
在鲁伯H35大鼠肝癌细胞的一个亚系中，该细胞在血清剥夺条件下会进入静止状态，而胰岛素在此发挥生长因子的作用。当将其添加到血清剥夺的H35细胞中时，生理浓度的胰岛素会刺激DNA合成，这表明仅胰岛素就能够诱导细胞从G0/G1期转变为S期。这种由纳摩尔浓度胰岛素诱导的反应是直接通过胰岛素受体介导的。在此我们表明，与这种生长反应同时发生的是，胰岛素或血清会使血清剥夺的H35细胞中c-fos和c-myc mRNA的稳态水平急剧增加，其时间进程与在再生肝脏中观察到的相似。其他生长因子，包括表皮生长因子，似乎在DNA合成或c-myc mRNA诱导方面对这些细胞没有影响。佛波酯佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA）也能诱导c-myc和c-fos mRNA，但不诱导DNA合成。然而，这种诱导机制似乎与胰岛素诱导的机制不同，因为用PMA预处理细胞仅会阻断PMA介导的而非胰岛素介导的c-myc和c-fos诱导。
