beta-catenin is a downstream effector of Wnt-mediated tumorigenesis in themammary gland

The Wnt signal transduction pathway has been implicated in mammary tumorige nesis in the mouse. beta -catenin, a key downstream effector of this pathwa y interacts with and thus activates the Tcf/Lef family of transcription fac tors. Elevated levels of beta -catenin have been found in many human tumors , notably colon carcinomas. Recently, elevated levels of beta -catenin have been associated with poor prognosis in human adenocarcinoma of the breast. In order to assess the possible role of beta -catenin in mammary carcinoma , we have created transgenic mice bearing the MMTV-LTR driving an activated form of beta -catenin. These mice develop mammary gland hyperplasia and ma mmary adenocarcinoma, a phenotype very similar to that of transgenic mice e xpressing an MMTV-driven Writ gene. Indeed, the histopathology of the mamma ry tumors in Wnt-mediated adenocarcinoma is identical to that observed in o ur beta -catenin-mediated disease model. Furthermore, putative beta -cateni n transcriptional targets, cyclin D1 and c-myc, are elevated in beta -caten in-mediated mammary tumors and cell lines. These observations support the n otion that the oncogenic Wnt pathway operates via beta -catenin and its tar gets in the context of mammary hyperplasia and carcinoma.