c-myc as a mediator of accelerated apoptosis and involution in mammary glands lacking Socs3
| Autor: | Jane E. Visvader, Christine J. Watson, Sheridan L Holroyd, Lewis A. Chodosh, Warren S. Alexander, Edward J. McManus, François Vaillant, Geoffrey J. Lindeman, Natasha C. Forrest, Kate D. Sutherland, Tim M. Wintermantel, Günther Schütz |
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| Jazyk: | angličtina |
| Rok vydání: | 2006 |
| Předmět: |
STAT3 Transcription Factor
Mammary gland Apoptosis Suppressor of Cytokine Signaling Proteins Suppressor of cytokine signalling Leukemia Inhibitory Factor Models Biological General Biochemistry Genetics and Molecular Biology Article Proto-Oncogene Proteins c-myc Mice Bcl-2-associated X protein Mammary Glands Animal medicine Animals Lactation Involution (medicine) SOCS3 Molecular Biology bcl-2-Associated X Protein General Immunology and Microbiology biology Integrases General Neuroscience digestive oral and skin physiology Epithelial Cells Phenotype Prolactin Matrix Metalloproteinases Enzyme Activation medicine.anatomical_structure bcl-2 Homologous Antagonist-Killer Protein Suppressor of Cytokine Signaling 3 Protein Gene Targeting biology.protein Cancer research Female Proto-Oncogene Proteins c-akt Bcl-2 Homologous Antagonist-Killer Protein Gene Deletion |
| Popis: | Suppressor of cytokine signalling (SOCS) proteins are critical attenuators of cytokine-mediated signalling in diverse tissues. To determine the importance of Socs3 in mammary development, we generated mice in which Socs3 was deleted in mammary epithelial cells. No overt phenotype was evident during pregnancy and lactation, indicating that Socs3 is not a key physiological regulator of prolactin signalling. However, Socs3-deficient mammary glands exhibited a profound increase in epithelial apoptosis and tissue remodelling, resulting in precocious involution. This phenotype was accompanied by augmented Stat3 activation and a marked increase in the level of c-myc. Moreover, induction of c-myc before weaning using an inducible transgenic model recapitulated the Socs3 phenotype, and elevated expression of likely c-myc target genes, E2F-1, Bax and p53, was observed. Our data establish Socs3 as a critical attenuator of pro-apoptotic pathways that act in the developing mammary gland and provide evidence that c-myc regulates apoptosis during involution. |
| Databáze: | OpenAIRE |
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