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PTEN Deletion and Concomitant c-Myc Activation Do Not Lead to Tumor Formation in Pancreatic beta Cells

Radziszewska, A; Choi, D; Nguyen, KTT; Schroer, SA; Tajmir, P; Wang, L; Suzuki, A; ... Woo, M; + view all (2009) PTEN Deletion and Concomitant c-Myc Activation Do Not Lead to Tumor Formation in Pancreatic beta Cells. J BIOL CHEM , 284 (5) 2917 - 2922. 10.1074/jbc.M805183200. Gold open access

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 beta cells leads to increased beta cell mass and protection from streptozotocin-induced diabetes. Importantly, PTEN deletion does not lead to tumor formation in beta 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 beta cell-specific PTEN knock-out mice expressing an inducible c-Myc transgene in beta 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 beta cells, there was no evidence of tumor development with sustained c-Myc activation.

Type: Article
Title: PTEN Deletion and Concomitant c-Myc Activation Do Not Lead to Tumor Formation in Pancreatic beta Cells
Open access status: An open access publication
DOI: 10.1074/jbc.M805183200
Keywords: INDUCED APOPTOSIS, GENE, BINDING, BAD, SUPPRESSOR, RESISTANCE, PROTEINS, PATHWAY, DOMAIN, SIGNAL
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation
URI: http://discovery.ucl.ac.uk/id/eprint/62078
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