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

Activation of the Writ 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 beta-catenin. Here, we analyze the activity of the Writ pathway in cultured cells derived from ductal and acinar pancreatic adenocarcinomas using a reporter assay dependent on the activity of the beta-catenin/Tcf4 complex. We find that low-level Writ 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 beta-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 catenin-dependent reporter activity, supporting the functional relevance of this mutation. Our findings indicate that activation of the Writ 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 Writ pathway components in the development/progression of tumors of the peripancreatic region merit consideration. (c) 2005 Elsevier B.V. All rights reserved.