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Department of Oncogene Research, Research Institute of Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan

The c-src proto-oncogene product, c-Src, is frequently over-expressed and activated in various human malignant cancers, implicating a role for c-Src in cancer progression. To verify the role of c-Src, we analyzed the transforming ability of c-Src in mouse embryonic fibroblasts that lack Csk, a negative regulator of Src family kinases. Although Csk deficiency is not sufficient for cell transformation, c-Src over-expression induced characteristic transformed phenotypes including anchorage-independent growth and tumorigenecity. These phenotypes were dose-dependently inhibited by the re-expression of Csk, indicating that there is a certain threshold for c-Src transformation, which is determined by the c-Src : Csk ratio. In contrast to v-Src, c-Src induced the phosphorylation of a limited number of cellular proteins and elicited a restricted change in gene expression profiles. The activation of some critical targets for v-Src transformation, such as STAT3, was not significantly induced by c-Src transformation. Several genes that are involved in cancer progression, that is, cyclin D1 and HIF-1, were induced by v-Src, but not by c-Src. Furthermore, v-Src tumors exhibited aggressive growth and extensive angiogenesis, while c-Src tumors grew more slowly accompanied by the induction of hematomas. These findings demonstrate that c-Src has the potential to induce cell transformation, but it requires coordination with an additional pathway(s) to promote tumor progression in vivo.

^* Correspondence: E-mail: okadam{at}biken.osaka-u.ac.jp

This article has been cited by other articles:

				C. Oneyama, T. Iino, K. Saito, K. Suzuki, A. Ogawa, and M. Okada Transforming Potential of Src Family Kinases Is Limited by the Cholesterol-Enriched Membrane Microdomain Mol. Cell. Biol., December 15, 2009; 29(24): 6462 - 6472. [Abstract] [Full Text] [PDF]