Fiche publication
Date publication
mai 2018
Journal
The Journal of experimental medicine
Auteurs
Membres identifiés du Cancéropôle Est :
Dr METZGER Daniel
Tous les auteurs :
Parisotto M, Grelet E, El Bizri R, Dai Y, Terzic J, Eckert D, Gargowitsch L, Bornert JM, Metzger D
Lien Pubmed
Résumé
Genetic ablation of the tumor suppressor in prostatic epithelial cells (PECs) induces cell senescence. However, unlike oncogene-induced senescence, no hyperproliferation phase and no signs of DNA damage response (DDR) were observed in -deficient PECs; loss-induced senescence (PICS) was reported to be a novel type of cellular senescence. Our study reveals that ablation in prostatic luminal epithelial cells of adult mice stimulates PEC proliferation, followed by a progressive growth arrest with characteristics of cell senescence. Importantly, we also show that proliferating -deficient PECs undergo replication stress and mount a DDR leading to p53 stabilization, which is however delayed by Mdm2-mediated p53 down-regulation. Thus, even though -deficiency induces cellular senescence that restrains tumor progression, as it involves replication stress, strategies promoting loss-induced senescence are at risk for cancer prevention and therapy.
Référence
J. Exp. Med.. 2018 May 9;:
