Se. Pories et al., OVEREXPRESSION OF PP60(C-SRC) ELICITS INVASIVE BEHAVIOR IN RAT COLON EPITHELIAL-CELLS, Gastroenterology, 114(6), 1998, pp. 1287-1295
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.