Oncogene, 2001-08, Vol.20 (37), p.5093-5099
2001
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- Autor(en) / Beteiligte
- Titel
- β-catenin is a downstream effector of Wnt-mediated tumorigenesis in the mammary gland
- Ist Teil von
- Oncogene, 2001-08, Vol.20 (37), p.5093-5099
- Ort / Verlag
- Basingstoke: Nature Publishing
- Erscheinungsjahr
- 2001
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0950-9232eISSN: 1476-5594DOI: 10.1038/sj.onc.1204586Titel-ID: cdi_proquest_miscellaneous_71133510
- Format
- –
- Schlagworte
- Adenocarcinoma, Adenocarcinoma - etiology, Adenocarcinoma - genetics, Adenocarcinoma - metabolism, Animals, b-catenin, beta Catenin, Biological and medical sciences, Blotting, Northern, Breast, Breast cancer, c-Myc protein, Cancer, Cyclin D1, Cyclin D1 - metabolism, Cytoskeletal Proteins - metabolism, Gynecology. Andrology. Obstetrics, Hyperplasia, LEF/TCF protein, Luciferases - metabolism, Mammary gland, Mammary gland diseases, Mammary Neoplasms, Animal - etiology, Mammary Neoplasms, Animal - genetics, Mammary Neoplasms, Animal - metabolism, Medical sciences, Mice, Mice, Transgenic, Myc protein, Phenotypes, Proto-Oncogene Proteins - genetics, Proto-Oncogene Proteins - metabolism, Proto-Oncogene Proteins c-myc - metabolism, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, Time Factors, Tissue Distribution, Trans-Activators, Transcription factors, Transcription Factors - metabolism, Transcription, Genetic, Transfection, Transgenes, Transgenic animals, Transgenic mice, Tumor Cells, Cultured, Tumorigenesis, Tumors, Wnt gene, Wnt protein, Wnt Proteins, Zebrafish Proteins, β-Catenin