OVEREXPRESSION OF PP60(C-SRC) ELICITS INVASIVE BEHAVIOR IN RAT COLON EPITHELIAL-CELLS

Background & Aims: Src activation is reported as an early event found in preneoplastic colonic adenomas and in 70% of colon carcinomas. The aim of this study was to identify the biological consequences of c-src overexpression in rat colon epithelial cells. Methods: Introduction a nd overexpression of c-src in an immortalized rat colon epithelial cel l line was achieved using lipofection, Transfectants were tested for c hanges in growth and cell behavior using different in vitro assay syst ems. Results: Colon epithelial cells overexpressing c-src showed the a bility to form microcolonies in soft agar without acquiring tumorigeni c potential. In in vitro assays, c-src transfectants displayed a gain of invasive potential through Matrigel without an accompanying change in migrational ability. No discernible qualitative changes were observ ed in the phosphotyrosyl protein profile between c-src and v-src trans fectants. Assessment of the cadherin/catenin status in these cells rev ealed an intact, functional complex with no detectable tyrosine phosph orylation of different components of the complex. Conclusions: Overexp ression of c-src in an immortalized rat colon epithelial cell line doe s not elicit full neoplastic transformation but enhances anchorage-ind ependent growth and confers invasion capability. Increased invasion th rough Matrigel was not linked to inactivation of the cadherin complex in c-src transfectants.