Effect of cigarette smoke exposure and mutant Kras overexpression on pancreatic cell proliferation

Glauert,Howard P.; Elliott,R. Scott; Han,Sung Gu; Athey,Mark; Lee,Eun Y.; Gairola,C. Gary

doi:10.3892/ol.2017.5606

Effect of cigarette smoke exposure and mutant Kras overexpression on pancreatic cell proliferation

Authors:
- Howard P. Glauert
- R. Scott Elliott
- Sung Gu Han
- Mark Athey
- Eun Y. Lee
- C. Gary Gairola
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Affiliations: Division of Nutritional Sciences, Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY 40536, USA, Department of Food Science and Biotechnology of Animal Resources, Konkuk University, Seoul 05029, Republic of Korea, Department of Pathology and Laboratory Medicine, University of Kentucky, Lexington, KY 40536, USA, Department of Toxicology and Cancer Biology, University of Kentucky, Lexington, KY 40536, USA
Published online on: January 17, 2017 https://doi.org/10.3892/ol.2017.5606
Pages: 1939-1943

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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.

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