Glucocorticoid-Induced Impairment of Mammary Gland Involution Is Associated with STAT5 and STAT3 Signaling Modulation
| Autor: | Edith C. Kordon, Andrea G. Pozzi, Paola Y. Bertucci, Ana Quaglino, Adali Pecci |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
STAT3 Transcription Factor
medicine.medical_specialty Mammary gland DNA Fragmentation Leukemia Inhibitory Factor Dexamethasone Mice Mammary Glands Animal Endocrinology Glucocorticoid receptor Internal medicine Cytokine Receptor gp130 STAT5 Transcription Factor medicine Animals Lactation Involution (medicine) STAT3 Glucocorticoids Mammary gland involution Mice Inbred BALB C biology medicine.anatomical_structure Gene Expression Regulation biology.protein STAT protein Female Signal transduction hormones hormone substitutes and hormone antagonists Glucocorticoid Signal Transduction medicine.drug |
| Zdroj: | Endocrinology. 151:5730-5740 |
| ISSN: | 1945-7170 0013-7227 |
| Popis: | The mammary epithelium undergoes cyclical periods of cellular proliferation, differentiation, and regression. During lactation, the signal transducer and activator of transcription factor (STAT)-5A and the glucocorticoid receptor (GR) synergize to induce milk protein expression and also act as survival factors. During involution, STAT3 activation mediates epithelial cell apoptosis and mammary gland remodeling. It has been shown that the administration of glucocorticoids at weaning prevents epithelial cell death, probably by extracellular matrix breakdown prevention. Our results show that the synthetic glucocorticoid dexamethasone (DEX) modulates STAT5A and STAT3 signaling and inhibits apoptosis induction in postlactating mouse mammary glands, only when administered within the first 48 h upon cessation of suckling. DEX administration right after weaning delayed STAT5A inactivation and degradation, preserving gene expression of target genes as β-casein (bcas) and prolactin induced protein (pip). Weaning-triggered GR down-regulation is also delayed by the hormone treatment. Moreover, DEX administration delayed STAT3 activation and translocation into epithelial cells nuclei. In particular, DEX treatment impaired the increment in gene expression of signal transducer subunit gp130, normally up-regulated from lactation to involution and responsible for STAT3 activation. Therefore, the data shown herein indicate that glucocorticoids are able to modulate early involution by controlling the strong cross talk that GR, STAT5, and STAT3 pathways maintains in the mammary epithelium. |
| Databáze: | OpenAIRE |
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