p120-catenin is critical for the development of invasive lobular carcinoma in mice

• Verfasst von: Tenhagen, Milou [VerfasserIn]
• Verfasst von: Hofmann, Ilse [VerfasserIn]
• Titel: p120-catenin is critical for the development of invasive lobular carcinoma in mice
• Verf.angabe: 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
• E-Jahr: 2016
• Jahr: 13 July 2016
• Umfang: 8 S.
• Fussnoten: Gesehen am 11.04.2019
• Titel Quelle: Enthalten in: Journal of mammary gland biology and neoplasia
• Ort Quelle: Dordrecht [u.a.] : Springer Science + Business Media B.V, 1996
• Jahr Quelle: 2016
• Band/Heft Quelle: 21(2016), 3, Seite 81-88
• ISSN Quelle: 1573-7039
• DOI: doi:10.1007/s10911-016-9358-3
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Invasive lobular carcinoma
• Sach-SW: Mouse model
• Sach-SW: p120
• K10plus-PPN: 1663114781

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.