p120-Catenin Is Critical for the Development of Invasive Lobular Carcinoma in Mice

J Mammary Gland Biol Neoplasia. 2016 Dec;21(3-4):81-88. doi: 10.1007/s10911-016-9358-3. Epub 2016 Jul 13.

Abstract

Loss of E-cadherin expression is causal to the development of invasive lobular breast carcinoma (ILC). E-cadherin loss leads to dismantling of the adherens junction and subsequent translocation of p120-catenin (p120) to the cytosol and nucleus. Although p120 is critical for the metastatic potential of ILC through the regulation of Rock-dependent anoikis resistance, it remains unknown whether p120 also contributes to ILC development. Using genetically engineered mouse models with mammary gland-specific inactivation of E-cadherin, p120 and p53, we demonstrate that ILC formation induced by E-cadherin and p53 loss is severely impaired upon concomitant inactivation of p120. Tumors that developed in the triple-knockout mice were mostly basal sarcomatoid carcinomas that displayed overt nuclear atypia and multinucleation. In line with the strong reduction in ILC incidence in triple-knockout mice compared to E-cadherin and p53 double-knockout mice, no functional redundancy of p120 family members was observed in mouse ILC development, as expression and localization of ARVCF, p0071 or δ-catenin was unaltered in ILCs from triple-knockout mice. In conclusion, we show that loss of p120 in the context of the p53-deficient mouse models is dominant over E-cadherin inactivation and its inactivation promotes the development of basal, epithelial-to-mesenchymal-transition (EMT)-type invasive mammary tumors.

Keywords: Breast cancer; Invasive lobular carcinoma; Mouse model; p120.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cadherins / metabolism*
  • Carcinoma, Lobular / metabolism*
  • Carcinoma, Lobular / pathology*
  • Catenins / metabolism*
  • Cell Nucleus / metabolism
  • Cytosol / metabolism
  • Female
  • Mammary Neoplasms, Experimental / metabolism*
  • Mammary Neoplasms, Experimental / pathology*
  • Mice
  • Mice, Knockout
  • Neoplasm Invasiveness
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Cadherins
  • Catenins
  • Tumor Suppressor Protein p53
  • delta catenin