TY  - JOUR
AU  - Tenhagen, Milou
AU  - Klarenbeek, Sjoerd
AU  - Braumuller, Tanya M
AU  - Hofmann, Ilse
AU  - van der Groep, Petra
AU  - Ter Hoeve, Natalie
AU  - van der Wall, Elsken
AU  - Jonkers, Jos
AU  - Derksen, Patrick W B
TI  - p120-Catenin Is Critical for the Development of Invasive Lobular Carcinoma in Mice.
JO  - Journal of mammary gland biology and neoplasia
VL  - 21
IS  - 3-4
SN  - 1573-7039
CY  - Dordrecht [u.a.]
PB  - Springer Science + Business Media B.V
M1  - DKFZ-2017-05736
SP  - 81 - 88
PY  - 2016
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:27411687
C2  - pmc:PMC5159444
DO  - DOI:10.1007/s10911-016-9358-3
UR  - https://inrepo02.dkfz.de/record/130658
ER  -