| First Author | Tenhagen M | Year | 2016 |
| Journal | J Mammary Gland Biol Neoplasia | Volume | 21 |
| Issue | 3-4 | Pages | 81-88 |
| PubMed ID | 27411687 | Mgi Jnum | J:244972 |
| Mgi Id | MGI:5913751 | Doi | 10.1007/s10911-016-9358-3 |
| Citation | Tenhagen M, et al. (2016) p120-Catenin Is Critical for the Development of Invasive Lobular Carcinoma in Mice. J Mammary Gland Biol Neoplasia 21(3-4):81-88 |
| abstractText | 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 delta-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. |
