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

Milou Tenhagen, Sjoerd Klarenbeek, Tanya M Braumuller, Ilse Hofmann, Petra van der Groep, Natalie Ter Hoeve, Elsken van der Wall, Jos Jonkers, Patrick W B Derksen

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)81-88
Number of pages8
JournalJournal of Mammary Gland Biology and Neoplasia
Volume21
Issue number3-4
DOIs
Publication statusPublished - Dec 2016

Keywords

  • p120
  • Mouse model
  • Breast cancer
  • Invasive lobular carcinoma

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