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 journalArticlepeer-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 (US)
Pages (from-to)81-88
Number of pages8
JournalJournal of Mammary Gland Biology and Neoplasia
Volume21
Issue number3-4
DOIs
StatePublished - Dec 1 2016

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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