Deregulated ephrin-B2 expression in the mammary gland interferes with the development of both the glandular epithelium and vasculature and promotes metastasis formation

Haldimann, Mirjam; Custer, Domenica; Munarini, Nadia; Stirnimann, Christoph; Zürcher, Gisela; Rohrbach, Valeria; Djonov, Valentin; Ziemiecki, Andrew; Andres, Anne-Catherine (2009). Deregulated ephrin-B2 expression in the mammary gland interferes with the development of both the glandular epithelium and vasculature and promotes metastasis formation. International journal of oncology, 35(3), pp. 525-36. Athens: Spandidos Publications 10.3892/ijo_00000364

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Eph receptor tyrosine kinases and their membrane-bound ephrin ligands play key roles during morphogenesis and adult tissue homeostasis. Receptor-ligand interactions result in forward and reverse signalling from the receptor and ligand respectively. To delineate the role(s) of forward and reverse signalling in mammary gland biology we have established transgenic mice exhibiting mammary epithelial-specific overexpression of either the native ephrin-B2 or a dominant negative ephrin-B2 mutant incapable of reverse signalling. During pregnancy and lactation overexpression of the native ephrin-B2 resulted in precocious differentiation, whereas overexpression of mutated ephrin-B2 caused delayed epithelial differentiation and in disturbed tissue architecture. Both transgenes affected also mammary vascularisation. Whereas ephrin-B2 induced superfluous but organised capillaries, mutant ephrin-B2 overexpression resulted in an irregular vasculature with blind-ending capillaries. Mammary tumours were not observed in either transgenic line, however, the crossing with NeuT transgenic animals revealed that mutated ephrin-B2 expression significantly accelerated tumour growth and imposed a metastatic phenotype.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DCR Unit Tiefenau Hospital (discontinued) > Forschungsgruppe Biologie und Karzinogenese der Brustdrüse (discontinued)

UniBE Contributor:

Rohrbach, Valeria; Ziemiecki, Andrew and Andres, Anne Catherine

ISSN:

1019-6439

Publisher:

Spandidos Publications

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 15:13

Last Modified:

04 May 2014 23:23

Publisher DOI:

10.3892/ijo_00000364

PubMed ID:

19639173

Web of Science ID:

000268736400008

URI:

https://boris.unibe.ch/id/eprint/32337 (FactScience: 197434)

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