Document Detail


Altered mammary epithelial development, pattern formation and involution in transgenic mice expressing the EphB4 receptor tyrosine kinase.
MedLine Citation:
PMID:  11801721     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We have previously documented the cell-type-specific and hormone-dependent expression of the EphB4 receptor in the mouse mammary gland. To investigate its role in the biology of the mammary gland, we have established transgenic mice bearing the EphB4 receptor under the control of the MMTV-LTR promoter, which represents the first transgenic mouse model to investigate the effect(s) of unscheduled expression of EphB4 in adult organisms. Transgene expression in the mammary epithelium was induced at puberty, increased during pregnancy, culminated at early lactation and persisted until day three of post-lactational involution. In contrast, expression of the endogenous EphB4 gene is downregulated during pregnancy, is essentially absent during lactation and is re-induced after day three of post-lactational involution. The unscheduled expression of EphB4 led to a delayed development of the mammary epithelium at puberty and during pregnancy. During pregnancy, less lobules were formed, these however exhibited more numerous but smaller alveolar units. Transgenic mammary glands were characterized by a fragile, irregular morphology at lactation; however, sufficient functionality was maintained to nourish the young. Transgenic mammary glands exhibited untimely epithelial apoptotic cell death during pregnancy and abnormal epithelial DNA synthesis at early post-lactational involution, indicating a disturbed response to proliferative/apoptotic signals. Mammary tumours were not observed in the EphB4 transgenic animals; however, in double transgenic animals expressing both EphB4 and the neuT genes, tumour appearance was significantly accelerated and, in contrast to neuT-only animals, metastases were observed in the lung. These results implicate EphB4 in the regulation of tissue architecture, cellular growth response and establishment of the invasive phenotype in the adult mammary gland.
Authors:
Nadia Munarini; Richard Jäger; Susanne Abderhalden; Gisela Zuercher; Valeria Rohrbach; Saemi Loercher; Brigitte Pfanner-Meyer; Anne-Catherine Andres; Andrew Ziemiecki
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cell science     Volume:  115     ISSN:  0021-9533     ISO Abbreviation:  J. Cell. Sci.     Publication Date:  2002 Jan 
Date Detail:
Created Date:  2002-01-21     Completed Date:  2002-04-30     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0052457     Medline TA:  J Cell Sci     Country:  England    
Other Details:
Languages:  eng     Pagination:  25-37     Citation Subset:  IM    
Affiliation:
Department of Clinical Research, University of Berne, Tiefenaustrasse 120, CH-3004 Bern, Switzerland.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis
Blotting, Western
Body Patterning
Breast Neoplasms / genetics,  pathology
Cell Division
DNA / biosynthesis
Epithelial Cells / metabolism
Female
Gene Expression Regulation, Developmental
Immunohistochemistry
Lactation / physiology
Lung Neoplasms / secondary
Mammary Glands, Animal / cytology,  growth & development*,  metabolism*,  physiology
Mice
Mice, Transgenic
Phenotype
Pregnancy
Promoter Regions, Genetic
RNA / analysis
Receptor Protein-Tyrosine Kinases / genetics,  immunology,  metabolism*
Receptor, EphB4
Receptors, Eph Family
Chemical
Reg. No./Substance:
63231-63-0/RNA; 9007-49-2/DNA; EC 2.7.10.1/Receptor Protein-Tyrosine Kinases; EC 2.7.10.1/Receptor, EphB4; EC 2.7.10.1/Receptors, Eph Family

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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