An Insulin-like Growth Factor-mediated, Phosphatidylinositol 3′ Kinase-independent Survival Signaling Pathway in β Tumor Cells

Hyperproliferation of tumor cells usually coincides with increased tumor cell apoptosis. To overcome apoptosis, tumor cells frequently induce the expression of growth factors that mediate cell survival. In nontransformed cells, including fibroblasts and neurons, survival factor-mediated signal transduction involves the activation of phosphatidylinositol 3′ kinase (PI-3K) and protein kinase B/c-Akt (PKB). Here we demonstrate that tumor cell lines derived from a transgenic mouse model of pancreatic β cell carcinogenesis use insulin-like growth factors to repress apoptosis independently of PI-3K and PKB. The results indicate that tumor cells can use additional survival signal transduction pathways.