p120-Catenin Is Critical for the Development of Invasive Lobular Carcinoma in MiceReportar como inadecuado




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Journal of Mammary Gland Biology and Neoplasia

, Volume 21, Issue 3–4, pp 81–88

First Online: 13 July 2016Received: 30 March 2016Accepted: 29 June 2016DOI: 10.1007-s10911-016-9358-3

Cite this article as: Tenhagen, M., Klarenbeek, S., Braumuller, T.M. et al. J Mammary Gland Biol Neoplasia 2016 21: 81. doi:10.1007-s10911-016-9358-3

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.

Keywordsp120 Mouse model Breast cancer Invasive lobular carcinoma Electronic supplementary materialThe online version of this article doi:10.1007-s10911-016-9358-3 contains supplementary material, which is available to authorized users.

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Autor: Milou Tenhagen - Sjoerd Klarenbeek - Tanya M. Braumuller - Ilse Hofmann - Petra van der Groep - Natalie ter Hoeve - Elske

Fuente: https://link.springer.com/







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