Department of Microbiology and Immunology, Queen's University, Botterell Hall, Rm. 713, Kingston, Ontario K7L3N6, Canada.
Anticancer Res. 2010 Jan;30(1):47-53.
To investigate the role of the cellular protooncogene product, cSrc, in neoplastic transformation by the large tumor antigen of simian virus 40 (TAg), the ability of TAg to increase cSrc activity was examined.
cSrc activity was measured in cells expressing wild-type or mutant TAg and compared to the parental line.
The results indicated that TAg expression in mouse 3T3 fibroblasts causes a dramatic increase in cSrc activity, a finding which establishes TAg as a cSrc activator. This ability depended upon a TAg, intact retinoblastoma-susceptibility gene product (Rb) family-binding site. In addition, genetic ablation of pRb in mouse fibroblasts increased cSrc activity, suggesting that pRb inactivation by TAg might be responsible for the observed cSrc activation. Furthermore, down-regulation or genetic ablation of cSrc alone, or together with the Src family members, Yes and Fyn, caused a dramatic reduction in the ability of TAg to transform mouse fibroblasts.
Taken together, these findings suggest for the first time that cSrc is part of an important pathway emanating from TAg and leading to neoplastic conversion.
研究细胞原癌基因产物 cSrc 在猴病毒 40 （SV40 ）大肿瘤抗原（TAg ）引起的肿瘤转化中的作用，检测 TAg 是否能增加 cSrc 的活性。
检测表达野生型或突变型 TAg 的细胞中的 cSrc 活性，并与亲本细胞系进行比较。
结果表明，TAg 在小鼠 3T3 成纤维细胞中的表达导致 cSrc 活性显著增加，这一发现确立了 TAg 作为 cSrc 激活剂的作用。这种能力依赖于 TAg 完整的视网膜母细胞瘤易感基因产物（Rb ）家族结合位点。此外，在小鼠成纤维细胞中遗传缺失 pRb 会增加 cSrc 活性，表明 TAg 对 pRb 的失活可能是导致观察到的 cSrc 激活的原因。此外，单独下调或遗传缺失 cSrc ，或与 Src 家族成员 Yes 和 Fyn 一起，会显著降低 TAg 转化小鼠成纤维细胞的能力。
这些发现表明，cSrc 是 TAg 诱导的导致肿瘤转化的重要信号通路的一部分。
