agar and Carcinoma--Pancreatic-Ductal

Increased levels of NF-κB are hallmarks of pancreatic ductal adenocarcinoma (PDAC) and both classical and alternative NF-κB activation pathways have been implicated.. Here we show that activation of the alternative pathway is a source for the high basal NF-κB activity in PDAC cell lines. Increased activity of the p52/RelB NF-κB complex is mediated through stabilization and activation of NF-κB-inducing kinase (NIK). We identify proteasomal downregulation of TNF receptor-associated factor 2 (TRAF2) as a mechanism by which levels of active NIK are increased in PDAC cell lines. Such upregulation of NIK expression and activity levels relays to increased proliferation and anchorage-independent growth, but not migration or survival of PDAC cells.. Rapid growth is one characteristic of pancreatic cancer. Our data indicates that the TRAF2/NIK/NF-κB2 pathway regulates PDAC cell tumorigenicity and could be a valuable target for therapy of this cancer.

Topics: Agar; Carcinoma, Pancreatic Ductal; Cell Line, Tumor; Cell Movement; Cell Nucleus; Cell Proliferation; Chemotaxis; Down-Regulation; Gene Expression Regulation, Neoplastic; Humans; NF-kappa B p52 Subunit; NF-kappaB-Inducing Kinase; Pancreatic Neoplasms; Proteasome Endopeptidase Complex; Protein Binding; Protein Serine-Threonine Kinases; Tetrazolium Salts; Thiazoles; TNF Receptor-Associated Factor 2