Bloch A, Liu X M, Wang L G
Department of Experimental Therapeutics, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Adv Enzyme Regul. 1995;35:35-41. doi: 10.1016/0065-2571(94)00019-y.
C-myb and c-ets-1 have variously been demonstrated to function as protooncogenes. Using a human leukemic cell line, ML-1, we have examined the mechanism by which these genes participate in establishing the sustained proliferation mode that is characteristic of the transformed cell. In the absence of serum, ML-1 cells were found to require IGF-1 and transferrin (TF) for growth and TGF-beta or TNF-alpha plus TF for differentiation. Upon administration of the growth factors, c-myb expression increased within 60 min, whereas after addition of the differentiation factors c-myb expression ceased completely within 3 hr. A correlation was found to exist between the level of c-ets-1 protein in the cells, the extent to which that protein is bound to intron I of the myb gene and the amount of c-myb mRNA that is expressed. Upon administration of growth factors, a sizable increase in the intracellular, and particularly, in the intranuclear level of c-ets-1 protein was observed, whereas a pronounced decrease in the level of this protein occurred after exposure to the differentiation factors. These data demonstrated that the level at which an oncogene-specified transcription factor is expressed can affect the expression of other target oncogenes involved in the regulation of cell proliferation. Stimulated expression of such transcription factor can then lead to the continuous proliferation cycle characteristic of the cancer cell.
C-myb和c-ets-1已被证实具有原癌基因的功能。利用人白血病细胞系ML-1，我们研究了这些基因参与建立转化细胞特有的持续增殖模式的机制。在无血清条件下，发现ML-1细胞生长需要胰岛素样生长因子-1（IGF-1）和转铁蛋白（TF），分化则需要转化生长因子-β（TGF-β）或肿瘤坏死因子-α（TNF-α）加TF。给予生长因子后，c-myb表达在60分钟内增加，而添加分化因子后，c-myb表达在3小时内完全停止。发现细胞中c-ets-1蛋白水平、该蛋白与myb基因内含子I的结合程度以及所表达的c-myb mRNA量之间存在相关性。给予生长因子后，观察到细胞内尤其是细胞核内c-ets-1蛋白水平显著增加，而暴露于分化因子后该蛋白水平明显下降。这些数据表明，癌基因特异性转录因子的表达水平可影响参与细胞增殖调控的其他靶癌基因的表达。这种转录因子的刺激表达随后可导致癌细胞特有的持续增殖周期。
