Beta1 integrins regulate mammary gland proliferation and maintain the integrity of mammary alveoli

Integrin-extracellular matrix interactions play important roles in the coordinated integration of external and internal cues that are essential for proper development. To study the role of beta1 integrin in the mammary gland, Itgbeta1(flox/flox) mice were crossed with WAPiCre transgenic mice, which...

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Bibliographic Details
Published in:The EMBO journal 2005-06, Vol.24 (11), p.1942-1953
Main Authors: Li, Na, Zhang, Yu, Naylor, Matthew J, Schatzmann, Franziska, Maurer, Francisca, Wintermantel, Tim, Schuetz, Gunther, Mueller, Ulrich, Streuli, Charles H, Hynes, Nancy E
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Basement Membrane - ultrastructure
Cell Cycle Proteins - biosynthesis
Cell Cycle Proteins - genetics
Cell Cycle Proteins - physiology
Cell Division
Cell Transformation, Neoplastic
Clone Cells - cytology
Crosses, Genetic
Cyclin-Dependent Kinase Inhibitor p21
DNA Replication
Epithelial Cells - cytology
Female
Focal Adhesion Kinase 1
Focal Adhesion Protein-Tyrosine Kinases
Gene Targeting
Integrin beta1 - genetics
Integrin beta1 - physiology
Lactation
Mammary Glands, Animal - abnormalities
Mammary Glands, Animal - cytology
Mammary Glands, Animal - transplantation
Mice
Mice, Knockout
Mice, Transgenic
Morphogenesis
Pregnancy
Protein-Tyrosine Kinases - biosynthesis
Protein-Tyrosine Kinases - genetics
Protein-Tyrosine Kinases - physiology
Stem Cells - cytology
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Summary:Integrin-extracellular matrix interactions play important roles in the coordinated integration of external and internal cues that are essential for proper development. To study the role of beta1 integrin in the mammary gland, Itgbeta1(flox/flox) mice were crossed with WAPiCre transgenic mice, which led to specific ablation of beta1 integrin in luminal alveolar epithelial cells. In the beta1 integrin mutant mammary gland, individual alveoli were disorganized resulting from alterations in cell-basement membrane associations. Activity of focal adhesion kinase (FAK) was also decreased in mutant mammary glands. Luminal cell proliferation was strongly inhibited in beta1 integrin mutant glands, which correlated with a specific increase of p21 Cip1 expression. In a p21 Cip1 null background, there was a partial rescue of BrdU incorporation, providing in vivo evidence linking p21 Cip1 to the proliferative defect observed in beta1 integrin mutant glands. A connection between p21 Cip1 and beta1 integrin as well as FAK was also established in primary mammary cells. These results point to the essential role of beta1 integrin signaling in mammary epithelial cell proliferation.
ISSN:0261-4189