Autophagy and unfolded protein response (UPR) regulate mammary gland involution by restraining apoptosis-driven irreversible changes

• DOI: 10.1038/s41420-018-0105-y
• Publication Date: 2018-09-25T14:31:06Z
• Authors: Anni Wärri; Katherine L. Cook; Rong Hu; Lu Jin; Alan Zwart; David R. Soto-Pan...; Jie Liu; Toren Finkel; Robert Clarke
• Keywords: Involution (esoterism)

The postnatal mammary gland undergoes repeated cycles of proliferation and cell death, most notably when the fully differentiated (lactating) dedifferentiates to a prelactation state. Accumulation milk proteins in secretory epithelium creates stress signal that triggers this process (involution). How is perceived, cellular processes are subsequently activated, remain unclear. We now report Unfolded Protein Response (UPR), autophagy, apoptosis related genes cluster separately during lactation involution mouse gland. Time-course experiments rodents show autophagy UPR signaling tightly co-regulated at transition from reversible irreversible involution. Inhibition by chloroquine or genetic deletion one ATG7 allele enhanced progression into phase, as characterized an early/precocious induction apoptosis. These first preclinical vivo data support clinical trial testing inhibitor for prevention intraductal breast malignancy invasive cancer. In marked contrast, stimulation low dose tunicamycin treatment reduced extended phase sustaining epithelium. Autophagy stimulators could be used short-term promote women experiencing difficulties irregularities nursing. Taken together, these indicate play key role regulating balance between survival normal regression.