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β-catenin is a downstream effector of Wnt-mediated tumorigenesis in the mammary gland

Oncogene volume 20, pages 5093–5099 (2001)Cite this article

Abstract

The Wnt signal transduction pathway has been implicated in mammary tumorigenesis in the mouse. β-catenin, a key downstream effector of this pathway interacts with and thus activates the Tcf/Lef family of transcription factors. Elevated levels of β-catenin have been found in many human tumors, notably colon carcinomas. Recently, elevated levels of β-catenin have been associated with poor prognosis in human adenocarcinoma of the breast. In order to assess the possible role of β-catenin in mammary carcinoma, we have created transgenic mice bearing the MMTV–LTR driving an activated form of β-catenin. These mice develop mammary gland hyperplasia and mammary adenocarcinoma, a phenotype very similar to that of transgenic mice expressing an MMTV-driven Wnt gene. Indeed, the histopathology of the mammary tumors in Wnt-mediated adenocarcinoma is identical to that observed in our β-catenin-mediated disease model. Furthermore, putative β-catenin transcriptional targets, cyclin D1 and c-myc, are elevated in β-catenin-mediated mammary tumors and cell lines. These observations support the notion that the oncogenic Wnt pathway operates via β-catenin and its targets in the context of mammary hyperplasia and carcinoma.

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Acknowledgements

We thank Anne Harrington for technical assistance in generating the transgenic mice. JS Michaelson is supported by a Breast Cancer Research Fellowship from the Department of Defense.

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  1. Department of Genetics, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, Massachusetts, USA

    Jennifer S Michaelson & Philip Leder

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  1. Jennifer S Michaelson
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Michaelson, J., Leder, P. β-catenin is a downstream effector of Wnt-mediated tumorigenesis in the mammary gland. Oncogene 20, 5093–5099 (2001). https://doi.org/10.1038/sj.onc.1204586

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