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

Oncogene. 2001 Aug 23;20(37):5093-9. doi: 10.1038/sj.onc.1204586.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenocarcinoma / etiology
  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism
  • Animals
  • Blotting, Northern
  • Cyclin D1 / metabolism
  • Cytoskeletal Proteins / metabolism*
  • Luciferases / metabolism
  • Mammary Neoplasms, Animal / etiology*
  • Mammary Neoplasms, Animal / genetics
  • Mammary Neoplasms, Animal / metabolism*
  • Mice
  • Mice, Transgenic
  • 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 / metabolism
  • Transcription, Genetic
  • Transfection
  • Transgenes
  • Tumor Cells, Cultured
  • Wnt Proteins
  • Zebrafish Proteins*
  • beta Catenin

Substances

  • CTNNB1 protein, mouse
  • Cytoskeletal Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-myc
  • Trans-Activators
  • Transcription Factors
  • Wnt Proteins
  • Zebrafish Proteins
  • beta Catenin
  • Cyclin D1
  • Luciferases