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- Title
Effect of cigarette smoke exposure and mutant Kras overexpression on pancreatic cell proliferation.
- Authors
GLAUERT, HOWARD P.; ELLIOTT, R. SCOTT; SUNG GU HAN; ATHEY, MARK; LEE, EUN Y.; GAIROLA, C. GARY
- Abstract
Pancreatic cancer is the fourth leading cause of cancer-associated mortality. The major risk factor for pancreatic cancer is cigarette smoking. Kras mutations are commonly observed in human pancreatic cancers. The present study examined the hypothesis that exposure to cigarette smoke and overexpression of a mutant Kras gene in the pancreas affects pancreatic cell proliferation in mice. Mice overexpressing the mutant Kras gene (KRasG12D) in the pancreas as well as wild-type mice were exposed to environmental tobacco smoke for 2 weeks. Overexpression of mutant Kras increased cell proliferation in pancreatic ductal, acinar and islet cells. Notably, cigarette smoke exposure decreased cell proliferation in pancreatic ductal and acinar cells, and had no effect in islet cells. Cigarette smoke did not affect pancreatic protein levels of tumor necrosis factor (TNF)α, p53, or cyclin D1, but mutant Kras overexpression slightly decreased TNFα and p53 protein levels. Therefore, pancreatic cell proliferation in mice overexpressing mutant Kras is associated with the later development of pancreatic tumors, but effects of cigarette smoke on pancreatic cell proliferation do not provide a good model for human pancreatic carcinogenesis.
- Subjects
CIGARETTE smoke; RISK factors of pancreatic cancer; PANCREATIC cancer genetics; GENETIC mutation; GENETIC overexpression
- Publication
Oncology Letters, 2017, Vol 13, Issue 3, p1939
- ISSN
1792-1074
- Publication type
Article
- DOI
10.3892/ol.2017.5606