deletion in luminal cells of mature prostate induces replication stress and senescence in vivo.
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;: