Beta1 integrins regulate mammary gland proliferation and maintain the integrity of mammary alveoli
| Autor: | Tim M. Wintermantel, Franziska Schatzmann, Ulrich Mueller, Yu Zhang, Gunther Schuetz, Nancy E. Hynes, Matthew J. Naylor, Na Li, Francisca G. Maurer, Charles H. Streuli |
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| Rok vydání: | 2004 |
| Předmět: |
Cyclin-Dependent Kinase Inhibitor p21
DNA Replication Cell division Mammary gland Morphogenesis Apoptosis Cell Cycle Proteins Mice Transgenic Biology General Biochemistry Genetics and Molecular Biology Basement Membrane Article Collagen receptor Focal adhesion Mice Mammary Glands Animal Pregnancy medicine Animals Lactation Molecular Biology Crosses Genetic Basement membrane Mice Knockout General Immunology and Microbiology General Neuroscience Integrin beta1 Stem Cells Epithelial Cells Protein-Tyrosine Kinases Epithelium Cell biology Clone Cells medicine.anatomical_structure Cell Transformation Neoplastic Focal Adhesion Kinase 1 Focal Adhesion Protein-Tyrosine Kinases Gene Targeting Cancer research Female Stem cell Cell Division |
| Zdroj: | The EMBO journal. 24(11) |
| ISSN: | 0261-4189 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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