RESEARCH ARTICLE Implications of Targeted Genomic Disruption of b-Catenin in BxPC-3

Pancreatic adenocarcinoma (PA) is among the most aggressive human tumors with an overall 5-year survival rate of,5 % and available treatments are only minimal effective. WNT/b-catenin signaling has been identified as one of 12 core signaling pathways that are commonly mutated in PA. To obtain more insight into the role of WNT/b-catenin signaling in PA we established human PA cell lines that are deficient of the central canonical WNT signaling protein b-catenin by using zinc-finger nuclease (ZFN) mediated targeted genomic disruption in the b-catenin gene (CTNNB1). Five individual CTNNB1 gene disrupted clones (BxPC3DCTNNB1) were established from a BxPC-3 founder cell line. Despite the complete absence of b-catenin, all clones displayed normal cell cycle distribution profiles, overall normal morphology and no elevated levels of apoptosis although increased doubling times were observed in three of the five BxPC3DCTNNB1 clones. This confirms that WNT/ b-catenin signaling is not mandatory for long term cell growth and survival in BxPC-3 cells. Despite a normal morphology of the b-catenin deficient cell lines, quantitativ