Pancreatic ductal adenocarcinoma (PDAC) is the 4th most common cause of cancer deaths in the United States. Due to the aggressive nature of this cancer and the lack of biomarkers for early detection, the incidence and mortality rates for PDAC are nearly equivalent. A better understanding of the molecular mechanisms leading to the development of pancreatic cancer remains a major goal for defining appropriate treatment strategies. Past studies have shown that the proto-oncogene Pim-3 kinase is expressed in pancreatic cancer and is able to phosphorylate the pro-apoptotic protein Bad to block Bad-mediated apoptosis in human pancreatic cancer cell lines. With these and other observations implicating Pim kinases as oncogenes and inhibitors of apoptosis, the purpose of our study is to further characterize the functional significance of Pim-3 in PDAC growth as well as identify possible downstream targets. We hypothesize that inhibition of Pim-3 signaling will be an effective approach for antagonizing the aberrant growth of pancreatic cancer. Initially, we confirmed by immunohistochemistry that Pim-3 protein is aberrantly expressed in human pancreatic cancer and pancreatitis tissue and is constitutively expressed in a panel of human pancreatic cancer cell lines. Also, we found that suppression of Pim-3 by shRNAs significantly decreased cell growth and caused a reduction in invasion of pancreatic cancer cells in Matrix-gel. To our knowledge, this is the first time that any of the Pims have been associated with invasion in pancreatic cancer. Most recently, other members of the Pim kinase family have been shown to activate NF-κB in cancer. From our studies, we observed that suppression of Pim-3 upregulated IκBα and decreased phospho-NF-κB p65 (Ser536), suggesting an effect on NF-κB transcription activity. Our results indicate the importance of Pim-3 in various aspects of transformation of pancreatic cancer and how NF-κB may be a potential downstream target of Pim-3 signaling in PDAC. These findings will allow us to critically validate Pim kinases as novel biomarkers and therapeutic targets for pancreatic cancer.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3104.