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

We have recently demonstrated that overexpression of PKCe is oncogenic in colonic epithelial cells. To test whether PI3K might be an upstream effector of PKCe in cell transformation, we have overexpressed the p110α PI3K subunit in non-transformed D/WT colonic epithelial cells. Transfectants displayed the major in vitro features of transformed cells. Interestingly, no transformation occurred when p110α was co-transfected with a dead-kinase PKCe mutant. The p85a subunit of PI3K, displaying a dominant-negative-like effect, was then transfected in PKCe-transformed D/e cells. The transformed profile of these cells was markedly reduced. To identify which by-products of PI3K might be involved in cell transformation we have transfected the D/WT cell line with cDNAs encoding the PI3 kinases hVps34 and C2β. Overexpression of hVps34 did not cause cell transformation. Conversely, in vitro transformation was observed when C2β was transfected into D/WT cells. These results indicate that phosphatidylinositol-3 monophosphate does not seem to be involved in cell transformation, and that phosphatidylinositol-3,4 bisphosphate and phosphatidylinositol-3,4,5 trisphosphate are more likely involved in this process. Thus, our data support the hypothesis of a linkage between PI3K and PKCe, and indicate that PI3K may act as a source of second messengers responsible for oncogenic activation of PKCe.