Abstract
Abstract
Pancreatic cancer is the leading cause of cancer mortality in both men and women in western countries due to its unresponsiveness to available therapeutics. It is well documented that smoking, diabetes and pancreatitis from chronic alcohol consumption are risk factors for this type of cancer. More than 95% of pancreatic cancers are pancreatic ductal adenocarcinomas (PDACs) that arise from pancreatic ductal epithelia. Our lab has previously shown that nicotine stimulates the proliferation and migration of human small airway epithelial cells and the adenocarcinomas derived from them in vitro due to nicotine induced changes in the sensitivity of the nicotinic acetylcholine receptors. Such changes caused an increase in the production and secretion of excitatory neurotransmitters, but decreased the production and secretion of inhibitory neurotransmitter γ-aminobutyric acid (GABA). In analogy to these findings in lung cells, both nicotine and ethanol stimulated cell proliferation in PDAC cell lines Panc-1 and BXPC-3 and in immortalized pancreatic duct epithelial cells HPDE6-C7. Acute and chronic treatment of all cell lines with nicotine or ethanol alone and in combination significantly increased the production of noradrenaline and adrenaline by the cells while significantly reducing GABA production. Western blots are currently underway to assess the potential modulation of nicotinic receptor protein expression as well signaling pathways. Our findings suggest a potential role for these pathways contributing to the development of smoking and alcohol related pancreatic carcinogenesis and may result in the identification of novel targets for the prevention and therapy of this malignancy.
Supported by R01CAo42829 with the National Cancer Institute.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1949. doi:10.1158/1538-7445.AM2011-1949