Involvement of PI3K in PKC epsilon-mediated oncogenic signal in rat colonic epithelial cells

We have recently demonstrated that overexpression of PKC epsilon is oncogen ic in colonic epithelial cells. To test whether PI3K might be an upstream e ffector of PKC epsilon in cell transformation, we have overexpressed the p1 10 alpha PI3K subunit in non-transformed D/WT colonic epithelial cells. Tra nsfectants displayed the major in vitro features of transformed cells. Inte restingly, no transformation occurred when p110 alpha was co-transfected wi th a dead-kinase PKC epsilon mutant. The p85 alpha subunit of PI3K, display ing a dominant-negative-like effect, was then transfected in PKC epsilon -t ransformed D/epsilon cells. The transformed profile of these cells was mark edly reduced. To identify which by-products of PI3K might be involved in ce ll transformation we have transfected the D/WT cell line with cDNAs encodin g the PI3 kinases hVps34 and C2 beta. Overexpression of hVps34 did not caus e cell transformation. Conversely, in vitro transformation was observed whe n C2 beta was transfected into D/WT cells. These results indicate that phos phatidylinositol-3 monophosphate does not seem to be involved in cell trans formation, and that phosphatidylinositol-3,4 bisphosphate and phosphatidyli nositol-3,4,5 trisphosphate are more likely involved in this process. Thus, our data support the hypothesis of a linkage between PI3K and PKC epsilon, and indicate that PI3K may act as a source of second messengers responsibl e for oncogenic activation of PKC epsilon.