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.