PTEN deletion and concomitant c-Myc activation do not lead to tumor formation in pancreatic β cells

Abstract

Phosphatase and tensin homologue (PTEN) deleted on chromosome 10 is a dual-specific phosphatase and a potent antagonist of the phosphoinositide 3-kinase signaling pathway. Although first discovered as a tumor suppressor, emerging evidence supports PTEN as a potential therapeutic target for diabetes. PTEN deletion in β cells leads to increased β cell mass and protection from streptozotocin-induced diabetes. Importantly, PTEN deletion does not lead to tumor formation in β cells. To further assess the potential tumorigenic role of PTEN, we tested the biological role of PTEN in the context of activation of the proto-oncogene c-Myc. We generated and characterized β cell-specific PTEN knock-out mice expressing an inducible c-Myc transgene in β cells. Surprisingly, we found that PTEN loss did not confer protection from the overwhelming apoptosis and diabetes development seen with c-Myc activation. Importantly, despite the combined effect of the loss of a tumor suppressor and activation of an oncogene in β cells, there was no evidence of tumor development with sustained c-Myc activation.