%0 Journal Article
%A Tenhagen, Milou
%A Klarenbeek, Sjoerd
%A Braumuller, Tanya M
%A Hofmann, Ilse
%A van der Groep, Petra
%A Ter Hoeve, Natalie
%A van der Wall, Elsken
%A Jonkers, Jos
%A Derksen, Patrick W B
%T p120-Catenin Is Critical for the Development of Invasive Lobular Carcinoma in Mice.
%J Journal of mammary gland biology and neoplasia
%V 21
%N 3-4
%@ 1573-7039
%C Dordrecht [u.a.]
%I Springer Science + Business Media B.V
%M DKFZ-2017-05736
%P 81 - 88
%D 2016
%X 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.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:27411687
%2 pmc:PMC5159444
%R 10.1007/s10911-016-9358-3
%U https://inrepo02.dkfz.de/record/130658