The Wnt pathway is active in a small subset of pancreas cancer cell lines

AbstractActivation of the Wnt pathway plays an important role in the development of a wide variety of tumor types. Two genes involved in the activation of this pathway in tumors are Adenomatous Polyposis Coli (APC) and β-catenin. Here, we analyze the activity of the Wnt pathway in cultured cells derived from ductal and acinar pancreatic adenocarcinomas using a reporter assay dependent on the activity of the β-catenin/Tcf4 complex. We find that low-level Wnt activity can be detected in several pancreas cancer lines. High levels of reporter activity were detected exclusively in RWP-1 cells. These cells display nuclear β-catenin and express a truncated APC protein resulting from a CAA>TAA mutation (Q1303X). Expression of a dominant negative Tcf4 protein inhibited proliferation of RWP-1 cells but not in other lines lacking β-catenin-dependent reporter activity, supporting the functional relevance of this mutation. Our findings indicate that activation of the Wnt pathway may play a role in a small subset of ductal pancreatic cancers. Alternatively, RWP-1 cells may have been derived from a tumor arising in a structure adjacent to the pancreas such as the biliary tract or the Ampulla of Vater. Additional studies on the role of Wnt pathway components in the development/progression of tumors of the peripancreatic region merit consideration