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J Mammary Gland Biol Neoplasia. 2016 Dec;21(3-4):81-88. Epub 2016 Jul 13.

p120-Catenin Is Critical for the Development of Invasive Lobular Carcinoma in Mice.

Author information

1
Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
2
Division of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
3
Vascular Oncology and Metastasis, German Cancer Research Center (DKFZ), Heidelberg, Germany.
4
Vascular Biology and Tumor Angiogenesis, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany.
5
Department of Medical Oncology, Cancer Center, UMC Utrecht, Utrecht, The Netherlands.
6
Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands. pderksen@umcutrecht.nl.

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.

KEYWORDS:

Breast cancer; Invasive lobular carcinoma; Mouse model; p120

PMID:
27411687
PMCID:
PMC5159444
DOI:
10.1007/s10911-016-9358-3
[Indexed for MEDLINE]
Free PMC Article

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