Increases in c-Src Expression Level and Activity Do Not Promote the Growth of Human Colorectal Carcinoma Cells In Vitro and In Vivo1*

The levels and activity of c-Src in colorectal cancer cells increasesteadilyduring thecourseof colorectal carcino-genesis and are most highly elevated in advanced metastatic disease. However, the effects of increases in c-Src activity on the proliferation of colorectal cancer cells during early and late stages of tumorigenesis re-main elusive. To study the consequences of increases in c-Src levels and activity on the growth of colorectal cancer cells in later stages of colorectal carcinogenesis, we developed human colorectal cancer cell lines in which c-Src levels and activity could be inducibly in-creased by a tightly controlled expression of wild-type c-Src or of the constitutively active mutant of c-Src, c-SrcY527F. Src induction activated multiple signaling pathways (often associated with a proliferative re-sponse) but promoted neither cell proliferation in vitro nor tumor growth in a xenograft model in vivo. These results indicate that, in more advanced stages of colo-rectal carcinogenesis, increases in c-Src levels and ac-tivity are likely to have functions other than the direct promotion of tumor growth