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Py2T murine breast cancer cells, a versatile model of TGFβ-induced EMT in vitro and in vivo

Waldmeier, L. and Meyer-Schaller, N. and Diepenbruck, M. and Christofori, G.. (2012) Py2T murine breast cancer cells, a versatile model of TGFβ-induced EMT in vitro and in vivo. PLoS ONE, Vol. 7, H. 11 , e48651.

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Official URL: http://edoc.unibas.ch/dok/A6338681

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Abstract

INTRODUCTION: Increasing evidence supports a role of an epithelial to mesenchymal transition (EMT) process in endowing subsets of tumor cells with properties driving malignant tumor progression and resistance to cancer therapy. To advance our understanding of the underlying mechanisms, we sought to generate a transplantable cellular model system that allows defined experimental manipulation and analysis of EMT in vitro and at the same time recapitulates oncogenic EMT in vivo. METHODOLOGY/RESULTS: We have established a stable murine breast cancer cell line (Py2T) from a breast tumor of an MMTV-PyMT transgenic mouse. Py2T cells display a metastable epithelial phenotype characterized by concomitant expression of luminal and basal cytokeratins and sheet migration. Exposure of Py2T cells to transforming growth factor beta (TGFbeta) in vitro induces reversible EMT accompanied by downregulation of E-cadherin and upregulation of mesenchymal markers, including EMT transcription factors, and a gain in single cell motility and invasiveness. Py2T cells give rise to tumors after orthotopic injection into syngeneic FVB/N mice. Notably, transplantation of epithelial Py2T cells results in the formation of invasive primary tumors with low to absent E-cadherin expression, indicating that the cells undergo EMT-like changes in vivo. This process appears to at least in part depend on TGFbeta signaling, since tumors formed by Py2T cells expressing a dominant-negative version of TGFbeta receptor widely maintain their epithelial differentiation status. CONCLUSIONS/SIGNIFICANCE: Together, the data demonstrate that the Py2T cell line represents a versatile model system to study the EMT process in vitro and in vivo. The observation that Py2T cells give rise to tumors and collectively undergo EMT-like changes in vivo highlights the suitability of the Py2T model system as a tool to study tumor-related EMT. In particular, Py2T cells may serve to corroborate recent findings relating EMT to cancer cell stemness, to therapy resistance and to tumor recurrence.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Division of Biochemistry and Genetics > Tumor Biology (Christofori)
UniBasel Contributors:Christofori, Gerhard M.
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Public Library of Science
e-ISSN:1932-6203
Note:Variant title: Py2T murine breast cancer cells, a versatile model of TGFbeta-induced EMT in vitro and in vivo -- Publication type according to Uni Basel Research Database: Journal article
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Last Modified:31 Aug 2018 06:40
Deposited On:08 May 2015 08:45

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