Autophagy and unfolded protein response (UPR) regulate mammary gland involution by restraining apoptosis-driven irreversible changes
| العنوان: | Autophagy and unfolded protein response (UPR) regulate mammary gland involution by restraining apoptosis-driven irreversible changes |
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| المؤلفون: | Jie Liu, Anni Wärri, Lu Jin, Rong Hu, Toren Finkel, David R. Soto-Pantoja, Alan Zwart, Robert Clarke, Katherine L. Cook |
| المصدر: | Cell Death Discovery, Vol 4, Iss 1, Pp 1-13 (2018) Cell Death Discovery |
| بيانات النشر: | Nature Publishing Group, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Cancer Research, Programmed cell death, Immunology, Mammary gland, Biology, lcsh:RC254-282, Article, 03 medical and health sciences, Cellular and Molecular Neuroscience, chemistry.chemical_compound, medicine, Involution (medicine), lcsh:QH573-671, Mammary gland involution, lcsh:Cytology, Autophagy, Cell Biology, Tunicamycin, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 3. Good health, Cell biology, 030104 developmental biology, medicine.anatomical_structure, chemistry, Apoptosis, Unfolded protein response |
| الوصف: | The postnatal mammary gland undergoes repeated cycles of proliferation and cell death, most notably when the fully differentiated (lactating) gland dedifferentiates to a prelactation state. Accumulation of milk proteins in the secretory epithelium creates the stress signal that triggers this process (involution). How this stress is perceived, and the cellular processes that are subsequently activated, remain unclear. We now report that Unfolded Protein Response (UPR), autophagy, and apoptosis related genes cluster separately during lactation and involution in the mouse mammary gland. Time-course experiments in rodents show that autophagy and UPR signaling are tightly co-regulated at the transition from reversible to irreversible involution. Inhibition of autophagy by chloroquine or genetic deletion of one ATG7 allele enhanced progression of mammary involution into the irreversible phase, as characterized by an early/precocious induction of apoptosis. These are the first preclinical in vivo data in support of a clinical trial testing an autophagy inhibitor for prevention of intraductal breast malignancy progression to invasive breast cancer. In marked contrast, stimulation of autophagy by low dose tunicamycin treatment reduced apoptosis and extended the reversible phase of involution by sustaining the secretory epithelium. Autophagy stimulators could be used short-term to promote lactation in women experiencing difficulties or irregularities in nursing. Taken together, these data indicate that UPR and autophagy play a key role in regulating the balance between cell survival and apoptosis during normal mammary gland regression. |
| اللغة: | English |
| تدمد: | 2058-7716 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2d9c980d6041cd29d12b4472c21a54b3Test http://link.springer.com/article/10.1038/s41420-018-0105-yTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....2d9c980d6041cd29d12b4472c21a54b3 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20587716 |
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