Beta-catenin and Tcfs in Mammary Development and Cancer

J Mammary Gland Biol Neoplasia. 2003 Apr;8(2):145-58. doi: 10.1023/a:1025944723047.

Abstract

Beta-catenin regulates cell-cell adhesion and transduces signals from many pathways to regulate the transcriptional activities of Tcf/Lef DNA binding factors. Gene ablation and transgenic expression studies strongly support the concept that beta-catenin together with Lef/Tcf factors act as a switch to determine cell fate and promote cell survival and proliferation at several stages during mammary gland development. Mice expressing the negative regulator of Wnt/beta-catenin signaling (K14-Dkk) fail to form mammary buds, and those lacking Lef-1 show an early arrest in this process at stage E13.5. Stabilized deltaN89beta-catenin initiates precocious alveologenesis during pubertal development, and negative regulators of endogenous beta-catenin signaling suppress normal alveologenesis during pregnancy. Stabilized beta-catenin induces hyperplasia and mammary tumors in mice. Each of the beta-catenin-induced phenotypes is accompanied by upregulation of the target genes cyclin D1 and c-myc. Cyclin D1, however, is dispensable for tumor formation and the initiation of alveologenesis but is essential for later alveolar expansion.

Publication types

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

MeSH terms

  • Animals
  • Breast Neoplasms / metabolism
  • Cadherins / metabolism
  • Cell Adhesion
  • Cell Division
  • Cell Survival
  • Cyclin D1 / metabolism
  • Cytoskeletal Proteins / metabolism
  • Cytoskeletal Proteins / physiology*
  • DNA-Binding Proteins / metabolism
  • DNA-Binding Proteins / physiology*
  • Female
  • Humans
  • Lymphoid Enhancer-Binding Factor 1
  • Mammary Glands, Animal / embryology
  • Mammary Glands, Human / embryology
  • Mammary Neoplasms, Animal / metabolism
  • Mice
  • Models, Biological
  • Mucin-1 / metabolism
  • Phenotype
  • Proto-Oncogene Proteins c-myc / metabolism
  • Signal Transduction
  • Trans-Activators / metabolism
  • Trans-Activators / physiology*
  • Transcription Factors / metabolism
  • Transcription Factors / physiology*
  • Up-Regulation
  • beta Catenin

Substances

  • CTNNB1 protein, human
  • CTNNB1 protein, mouse
  • Cadherins
  • Cytoskeletal Proteins
  • DNA-Binding Proteins
  • LEF1 protein, human
  • Lef1 protein, mouse
  • Lymphoid Enhancer-Binding Factor 1
  • Mucin-1
  • Proto-Oncogene Proteins c-myc
  • Trans-Activators
  • Transcription Factors
  • beta Catenin
  • Cyclin D1