Perturbation of beta1-integrin function in involuting mammary gland results in premature dedifferentiation of secretory epithelial cells
| Autor: | Jean Paul Thiery, Marisa M. Faraldo, Sylvie Tlouzeau, Marie-Ange Deugnier, Marina A. Glukhova |
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| Rok vydání: | 2002 |
| Předmět: |
Genetically modified mouse
Recombinant Fusion Proteins Dominant-Negative Mutant Mammary gland Apoptosis Mice Transgenic Article Mice Mammary Glands Animal In vivo Genes Reporter Pregnancy Proto-Oncogene Proteins medicine STAT5 Transcription Factor Animals Lactation RNA Messenger Promoter Regions Genetic Molecular Biology biology Integrin beta1 Mouse mammary tumor virus β1 integrin NF-kappa B Cell Differentiation Epithelial Cells Cell Biology Janus Kinase 2 Protein-Tyrosine Kinases biology.organism_classification Milk Proteins Molecular biology Cell biology DNA-Binding Proteins medicine.anatomical_structure Mammary Tumor Virus Mouse CD4 Antigens Trans-Activators Female Signal Transduction |
| Zdroj: | Molecular biology of the cell. 13(10) |
| ISSN: | 1059-1524 |
| Popis: | To study the mechanism of beta1-integrin function in vivo, we have generated transgenic mouse expressing a dominant negative mutant of beta1-integrin under the control of mouse mammary tumor virus (MMTV) promoter (MMTV-beta1-cyto). Mammary glands from MMTV-beta1-cyto transgenic females present significant growth defects during pregnancy and lactation and impaired differentiation of secretory epithelial cells at the onset of lactation. We report herein that perturbation of beta1-integrin function in involuting mammary gland induced precocious dedifferentiation of the secretory epithelium, as shown by the premature decrease in beta-casein and whey acidic protein mRNA levels, accompanied by inactivation of STAT5, a transcription factor essential for mammary gland development and up-regulation of nuclear factor-kappaB, a negative regulator of STAT5 signaling. This is the first study demonstrating in vivo that cell-extracellular matrix interactions involving beta1-integrins play an important role in the control of milk gene transcription and in the maintenance of the mammary epithelial cell differentiated state. |
| Databáze: | OpenAIRE |
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