Abstract 2358: MUC13 mucin augments pancreatic tumorigenesis

Abstract

Abstract Pancreatic cancer is one of the most lethal malignancies with extremely poor prognosis. The high death rate of pancreatic cancer is attributed to a lack of reliable methods of early diagnosis and underlying molecular mechanisms associated with aggressive pathogenesis. MUC13, a newly identified transmembrane mucin, is known to be aberrantly expressed in ovarian, gastric and colon cancer. However, the expression and functions of MUC13 in pancreatic cancer are unknown. Herein, we have investigated the expression and functions of MUC13 mucin, in pancreatic cancer to determine its potential for early cancer diagnosis and its role in pancreatic cancer pathogenesis. The expression profile of MUC13 in pancreatic cancer was investigated using a recently generated monoclonal antibody (MAb, clone PPZ0020) and pancreatic tissue microarrays. The expression of MUC13 was significantly (p<0.005) higher in cancer samples compared to the normal/non-neoplastic pancreatic tissues. For the functional analyses, a full length MUC13 gene cloned in pcDNA3.1 was expressed in MUC13 null pancreatic cancer cell lines, MiaPaca and Panc1. The exogenous MUC13 expression induced morphological changes, including scattering of cells. These changes were abrogated through c-jun NH2-terminal kinase (JNK) chemical inhibitor (SP600125) or JNK2 siRNA. Additionally, a marked reduction in cell-cell adhesion and significant (p<0.05) increases in cell motility, invasion, proliferation, clonogenicity and tumorigenesis in a xenograft mouse model system were observed upon exogenous MUC13 expression. These cellular characteristics were correlated with the up-regulation of HER2, p21-activated kinase1 (PAK1), extracellular signal-regulated kinase (ERK) and S100A4 (metastasin) and suppression of p53. Inhibition of MUC13 expression by MUC13 siRNA or shRNA resulted in suppression of tumorigenic characteristics in HPAFII pancreatic cancer cells. These results, for the first time, suggest that MUC13 expression augments pancreatic cancer progression and has potential as a diagnostic and/or therapeutic target. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 2358.