Hjelle B, Liu E, Bishop J M
Department of Microbiology and Immunology, University of California, San Francisco 94143.
Proc Natl Acad Sci U S A. 1988 Jun;85(12):4355-9. doi: 10.1073/pnas.85.12.4355.
The conversion of cells from a normal phenotype to full malignancy apparently requires multiple genetic events. Efforts to reconstruct multistep tumorigenesis in cell culture have shown that two types of oncogenes (typified by HRAS and MYC) can cooperate to elicit complete transformation. Transformation of embryonic rodent cells by single oncogenes is reputed either not to occur or to require specialized circumstances. It has not been known how the large group of oncogenes that encode protein-tyrosine kinases might fit into this scheme. We now report that v-src, a prototype for the kinase oncogenes, can convert rat embryo fibroblasts to a fully transformed and tumorigenic phenotype when the gene is expressed vigorously. By contrast, v-src had no demonstrable effect on diploid human fibroblasts. Our results sustain the view that it is possible for at least some oncogenes to achieve a potency sufficient for unilateral tumorigenesis.
细胞从正常表型转变为完全恶性状态显然需要多个基因事件。在细胞培养中重建多步骤肿瘤发生过程的研究表明,两种类型的癌基因(以HRAS和MYC为代表)可以协同作用引发完全转化。单个癌基因对胚胎啮齿动物细胞的转化据信要么不会发生,要么需要特殊情况。目前尚不清楚编码蛋白酪氨酸激酶的大量癌基因如何适用于这一模式。我们现在报告,激酶癌基因的原型v-src在基因强烈表达时可将大鼠胚胎成纤维细胞转化为完全转化且具有致瘤性的表型。相比之下,v-src对二倍体人成纤维细胞没有明显影响。我们的结果支持这样一种观点,即至少某些癌基因有可能获得足以导致单侧肿瘤发生的效力。