Inactivation of p53 function in cultured human mammary epithelial cells turns the telomere-length dependent senescence barrier from agonescence into crisis.

摘要: Cultured human mammary epithelial cells (HMEC) encounter two distinct barriers to indefinite growth. The first barrier, originally termed selection, can be overcome through loss of expression the cyclin-dependent kinase inhibitor p16(INK4A). resultant p16-, p53+ post-selection HMEC a second agonescence, associated with critically shortened telomeres and widespread chromosomal aberrations. Although some cell death is present at majority population retains long-term viability. We now show that abrogation p53 function in inactivates cycle checkpoints changes mostly viable agonescence barrier into crisis-like massive death. In contrast, inactivation does not affect ability barrier. These data indicate crisis represent different forms telomere-length dependent proliferation Altogether, our suggest modified model senescence barriers. propose Rb-mediated largely or completely independent telomere length. This being stasis, for stress-associated senescence. (agonescence crisis) results from ongoing erosion leading short dysfunction.