Does β-Catenin Cross-Regulate NFκB Signalling in Pancreatic Cancer and Chronic Pancreatitis?

BACKGROUND It is not clear by which mechanism nuclear factor-kappaB (NFκB) induces cell proliferation and escapes from the apoptotic pathway in pancreatic carcinogenesis. This study aimed to investigate β-catenin and NFκB signalling in chronic pancreatitis and pancreatic cancer. MATERIALS AND METHODS On tissue samples of chronic pancreatitis and pancreatic cancer, we performed immunohistochemistry for detecting the expression of tumour necrosis factor alpha (TNFα), β-catenin and NFκB, Western blot for TNFα, NFκB, β-catenin, c-Myc and FasL, co-immunoprecipitation for β-catenin with NFκB and RT-PCR for cyclin D1, c-Myc and Fas. RESULTS TNFα and NFκB expression was increased in chronic pancreatitis and pancreatic cancer. β-Catenin and cyclin D1 expression was intense in pancreatic cancer and moderate in chronic pancreatitis. Of the NFκB response elements, the expression of pro-proliferative c-Myc is intense in pancreatic cancer and moderate in chronic pancreatitis, but the pro-apoptotic factors, Fas and FasL were down-regulated in pancreatic cancer and moderately expressed in chronic pancreatitis. The co-immunoprecipitation results showed a significant interaction of β-catenin with NFκB in pancreatic cancer and a non-significant interaction in chronic pancreatitis. CONCLUSIONS β-Catenin might cross-regulate NFκB by interrupting the balance of cell death and cell survival via recruiting NFκB into the cell survival pathway alone in most cases of pancreatic cancer and some cases of chronic pancreatitis. © 2015 S. Karger AG, Basel.