Secreted signaling factors of the Wnt protein family regulate many cellular processes, including cell fate decisions and cell proliferation, and aberrant Wnt signaling is associated with tumorigenesis. Many Wnt proteins act via a signaling pathway that results in stabilization of beta-catenin and consequent transcriptional activation of specific target genes. Mutations in beta-catenin or other Wnt pathway components, which result in beta-catenin accumulation, are found in a wide range of human cancers. In contrast, such mutations have been found only rarely in breast cancer. Nevertheless there is strong evidence of stabilization of beta-catenin protein in a majority of human breast tumors. Moreover, studies in mouse model systems clearly demonstrate that activated Wnt signaling leads to mammary tumorigenesis. This review summarizes the current evidence implicating Wnt/beta-catenin signaling in breast cancer and discusses several possible mechanisms by which the pathway may become activated.
