beta-catenin is a downstream effector of Wnt-mediated tumorigenesis in the mammary gland.
The Wnt signal transduction pathway has been implicated in mammary tumorigenesis in the mouse. beta-catenin, a key downstream effector of this pathway interacts with and thus activates the Tcf/Lef family of transcription factors. 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 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 beta-catenin-mediated disease model. Furthermore, putative beta-catenin transcriptional targets, cyclin D1 and c-myc, are elevated in beta-catenin-mediated mammary tumors and cell lines. These observations support the notion that the oncogenic Wnt pathway operates via beta-catenin and its targets in the context of mammary hyperplasia and carcinoma.
Michaelson
J S
JS
Howard Hughes Medical Institute, Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Leder
P
P
D000230:Adenocarcinoma / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015152:Blotting, Northern; D019938:Cyclin D1 / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D008156:Luciferases / Q000378:metabolism; D015674:Mammary Neoplasms, Animal / Q000209:etiology* / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013997:Time Factors; D014018:Tissue Distribution; D015534:Trans-Activators; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D019076:Transgenes; D014407:Tumor Cells, Cultured; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin
C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D015534:Trans-Activators; D014157:Transcription Factors; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin; D019938:Cyclin D1; D008156:Luciferases