title: PTEN deletion and concomitant c-Myc activation do not lead to tumor formation in pancreatic beta 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 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.
authors.affiliation: Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G 2M9, Canada.
authors.forename: Anna
authors.initials: A
authors.lastname: Radziszewska
authors.affiliation: Institute of Medical Science, University of Toronto, Toronto, Ontario M5G 2M9, Canada.
authors.forename: Diana
authors.initials: D
authors.lastname: Choi
authors.affiliation: Institute of Medical Science, University of Toronto, Toronto, Ontario M5G 2M9, Canada.
authors.forename: Kinh-Tung T
authors.initials: KT
authors.lastname: Nguyen
authors.affiliation: Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G 2M9, Canada.
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Schroer
authors.affiliation: Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G 2M9, Canada.
authors.forename: Panteha
authors.initials: P
authors.lastname: Tajmir
authors.affiliation: Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G 2M9, Canada.
authors.forename: Linyuan
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Molecular Biology, Akita University School of Medicine, Akita 010-8543, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Suzuki
authors.affiliation: Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G 2M9, Canada; The Advanced Medical Discovery Institute, University of Toronto, Toronto, Ontario M5G 2C1, Canada.
authors.forename: Tak W
authors.initials: TW
authors.lastname: Mak
authors.affiliation: Cancer Research Institute and Department of Cellular and Molecular Pharmacology, Comprehensive Cancer Center, University of California at San Francisco, San Francisco, California 94143-0875.
authors.forename: Gerard I
authors.initials: GI
authors.lastname: Evan
authors.affiliation: Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G 2M9, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario M5G 2M9, Canada; Department of Medicine and Keenan Research Centre in the Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario M5B 1W8, Canada. Electronic address: mwoo@uhnresearch.ca.
authors.forename: Minna
authors.initials: M
authors.lastname: Woo
mesh_terms: D000818:Animals; D005260:Female; D017353:Gene Deletion; D016259:Genes, myc; D007150:Immunohistochemistry; D007515:Islets of Langerhans / Q000473:pathology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000502:physiology*; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D010766:Phosphorylation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D051025:bcl-Associated Death Protein / Q000378:metabolism
chemical_list: D051025:bcl-Associated Death Protein; D020928:Mitogen-Activated Protein Kinases; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse