Islet amyloid polypeptide does not suppress pancreatic cancer.

Autor:	Taylor AJ; BC Children's Hospital Research Institute, Vancouver, BC, Canada; Centre for Molecular Medicine and Therapeutics, Vancouver, BC, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, BC, Canada., Panzhinskiy E; Life Sciences Institute, University of British Columbia, BC, Canada; Department of Biochemistry, University of British Columbia, BC, Canada., Orban PC; BC Children's Hospital Research Institute, Vancouver, BC, Canada; Centre for Molecular Medicine and Therapeutics, Vancouver, BC, Canada; Department of Surgery, University of British Columbia, BC, Canada., Lynn FC; BC Children's Hospital Research Institute, Vancouver, BC, Canada; Department of Surgery, University of British Columbia, BC, Canada; Department of Cellular and Physiological Sciences, University of British Columbia, BC, Canada., Schaeffer DF; Department of Pathology and Laboratory Medicine, University of British Columbia, BC, Canada; Pancreas Centre BC, Vancouver, BC, Canada., Johnson JD; Life Sciences Institute, University of British Columbia, BC, Canada; Department of Cellular and Physiological Sciences, University of British Columbia, BC, Canada., Kopp JL; Life Sciences Institute, University of British Columbia, BC, Canada; Department of Cellular and Physiological Sciences, University of British Columbia, BC, Canada., Verchere CB; BC Children's Hospital Research Institute, Vancouver, BC, Canada; Centre for Molecular Medicine and Therapeutics, Vancouver, BC, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, BC, Canada; Department of Surgery, University of British Columbia, BC, Canada. Electronic address: bverchere@bcchr.ca.
Jazyk:	angličtina
Zdroj:	Molecular metabolism [Mol Metab] 2023 Feb; Vol. 68, pp. 101667. Date of Electronic Publication: 2023 Jan 05.
DOI:	10.1016/j.molmet.2023.101667
Abstrakt:	Objectives: Pancreatic cancer risk is elevated approximately two-fold in type 1 and type 2 diabetes. Islet amyloid polypeptide (IAPP) is an abundant beta-cell peptide hormone that declines with diabetes progression. IAPP has been reported to act as a tumour-suppressor in p53-deficient cancers capable of regressing tumour volumes. Given the decline of IAPP during diabetes development, we investigated the actions of IAPP in pancreatic ductal adenocarcinoma (PDAC; the most common form of pancreatic cancer) to determine if IAPP loss in diabetes may increase the risk of pancreatic cancer. Methods: PANC-1, MIA PaCa-2, and H1299 cells were treated with rodent IAPP, and the IAPP analogs pramlintide and davalintide, and assayed for changes in proliferation, death, and glycolysis. An IAPP-deficient mouse model of PDAC (Iapp -/- ; Kras +/LSL-G12D ; Trp53 flox/flox ; Ptf1a +/CreER ) was generated for survival analysis. Results: IAPP did not impact glycolysis in MIA PaCa-2 cells, and did not impact cell death, proliferation, or glycolysis in PANC-1 cells or in H1299 cells, which were previously reported as IAPP-sensitive. Iapp deletion in Kras +/LSL-G12D ; Trp53 flox/flox ; Ptf1a +/CreER mice had no effect on survival time to lethal tumour burden. Conclusions: In contrast to previous reports, we find that IAPP does not function as a tumour suppressor. This suggests that loss of IAPP signalling likely does not increase the risk of pancreatic cancer in individuals with diabetes. (Copyright © 2023 The Authors. Published by Elsevier GmbH.. All rights reserved.)
Databáze:	MEDLINE
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