Kanner S B, Parsons S J, Parsons J T, Gilmer T M
Department of Microbiology, University of Virginia School of Medicine, Charlottesville 22908.
Oncogene. 1988 Apr;2(4):327-35.
Tumor-derived Syrian hamster embryo (SHE) cell lines, induced in vitro by treatment with chemical carcinogens, contained increased levels of pp60c-src kinase activity compared to preneoplastic parental cell lines and normal SHE cells. The increased kinase activity did not result from an increase in the pp60c-src content of the SHE cell lines, but represented a 4-11 fold increase in pp60c-src kinase specific activity. Both the extent of phosphorylation and the velocity of pp60c-src phosphotransferase activity were increased in the tumor-derived cell lines. SHE cell lines producing chicken pp60c-src were isolated following co-transfection with plasmids bearing the chicken c-src and neoR genes. Chicken pp60c-src expressed in an asbestos-transformed, tumor-derived cell line showed an approximate 3-fold activation of tyrosine kinase activity compared to chicken pp60c-src expressed in the preneoplastic cell line. We suggest that these results indicate that activation of pp60c-src is mediated by trans-acting cellular factors present in the tumor-derived cells. Analysis of pp60c-src in normal SHE cells, preneoplastic cell lines and tumor-derived cell lines showed no alteration in the phosphorylation of tyr-527 or tyr-416, two tyrosine residues whose phosphorylation states have been associated with modulation of kinase activity. These studies indicate that the neoplastic progression of cells may be accompanied by the activation of proto-oncogene products, such as the pp60c-src tyrosine kinase, by mechanisms that may not directly involve genetic alteration of the proto-oncogene DNA sequence.
经化学致癌物处理后在体外诱导产生的肿瘤来源的叙利亚仓鼠胚胎（SHE）细胞系，与肿瘤前亲本细胞系和正常SHE细胞相比，其pp60c-src激酶活性水平升高。激酶活性的增加并非源于SHE细胞系中pp60c-src含量的增加，而是代表pp60c-src激酶比活性增加了4至11倍。在肿瘤来源的细胞系中，pp60c-src磷酸化的程度和磷酸转移酶活性的速度均增加。在用携带鸡c-src和neoR基因的质粒共转染后，分离出了产生鸡pp60c-src的SHE细胞系。与在肿瘤前细胞系中表达的鸡pp60c-src相比，在石棉转化的、肿瘤来源的细胞系中表达的鸡pp60c-src显示酪氨酸激酶活性有大约3倍的激活。我们认为，这些结果表明pp60c-src的激活是由肿瘤来源细胞中存在的反式作用细胞因子介导的。对正常SHE细胞、肿瘤前细胞系和肿瘤来源细胞系中的pp60c-src进行分析，发现tyr-527或tyr-416的磷酸化没有改变，这两个酪氨酸残基的磷酸化状态与激酶活性的调节有关。这些研究表明，细胞的肿瘤进展可能伴随着原癌基因产物（如pp60c-src酪氨酸激酶）的激活，其机制可能不直接涉及原癌基因DNA序列的遗传改变。
