Somatic Inactivation of E-cadherin and p53 in Mice Leads to Metastatic Lobular Mammary Carcinoma Through Induction of Anoikis Resistance and Angiogenesis

Cancer Cell. 2006 Nov;10(5):437-49. doi: 10.1016/j.ccr.2006.09.013.

Abstract

Metastatic disease is the primary cause of death in breast cancer, the most common malignancy in Western women. Loss of E-cadherin is associated with tumor metastasis, as well as with invasive lobular carcinoma (ILC), which accounts for 10%-15% of all breast cancers. To study the role of E-cadherin in breast oncogenesis, we have introduced conditional E-cadherin mutations into a mouse tumor model based on epithelium-specific knockout of p53. Combined loss of E-cadherin and p53 resulted in accelerated development of invasive and metastatic mammary carcinomas, which show strong resemblance to human ILC. Moreover, loss of E-cadherin induced anoikis resistance and facilitated angiogenesis, thus promoting metastatic disease. Our results suggest that loss of E-cadherin contributes to both mammary tumor initiation and metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anoikis / physiology*
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Breast Neoplasms / physiopathology
  • Cadherins / genetics
  • Cadherins / metabolism*
  • Carcinoma, Lobular / metabolism*
  • Carcinoma, Lobular / pathology
  • Carcinoma, Lobular / physiopathology
  • Disease Models, Animal
  • Female
  • Gene Silencing*
  • Humans
  • Mammary Glands, Human / anatomy & histology
  • Mammary Glands, Human / metabolism
  • Mammary Glands, Human / pathology
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Metastasis
  • Neovascularization, Pathologic
  • Skin Neoplasms / metabolism
  • Skin Neoplasms / pathology
  • Survival Rate
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • Cadherins
  • Tumor Suppressor Protein p53