Beta-catenin/Tcf activation partially mimics the transforming activity of Wnt-1 in Rat-1 fibroblasts

Abstract

We have previously demonstrated that Wnt-1 induction of cytosolic beta-catenin and Tcf/Lef transcriptional activation correlate with enhanced proliferation, survival, and post-confluent growth in Rat-1 fibroblasts. To examine whether beta-catenin mediates the biological responses to Wnt-1 in this context, we characterized Rat-1 clonal cell lines expressing different levels of a mutant, stabilized beta-catenin (beta-cateninS37A). Clonal lines exhibit elevated cytosolic and nuclear beta-cateninS37A and Tcf transcriptional activation, comparable to that elicited by Wnt-1 expression. However, expression of beta-cateninS37A does not promote growth of Rat-1 cells in serum-free conditions and only partially promotes growth post-confluence, when compared to that induced by Wnt-1 expression. As ectopic expression of beta-cateninS37A only partially mimics Wnt-1 effects on Rat-1 cells, we conclude that Wnt-1 signaling elicits biochemical events that act in addition to beta-catenin/Tcf signaling to promote cell growth.