Abstract
Aim: 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. Materials and Methods: cSrc activity was measured in cells expressing wild-type or mutant TAg and compared to the parental line. Results: 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. Conclusion: 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.
- cSrc
- Simian Virus 40 Large Tumor antigen
- retinoblastoma susceptibility gene product
- neoplastic transformation
- rodent fibroblasts
- signal transduction
Footnotes
- Received October 6, 2009.
- Revision received December 8, 2009.
- Accepted December 9, 2009.
- Copyright© 2010 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved