| First Author | Parisotto M | Year | 2018 |
| Journal | J Exp Med | Volume | 215 |
| Issue | 6 | Pages | 1749-1763 |
| PubMed ID | 29743291 | Mgi Jnum | J:265684 |
| Mgi Id | MGI:6193067 | Doi | 10.1084/jem.20171207 |
| Citation | Parisotto M, et al. (2018) PTEN deletion in luminal cells of mature prostate induces replication stress and senescence in vivo. J Exp Med 215(6):1749-1763 |
| abstractText | Genetic ablation of the tumor suppressor PTEN 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 PTEN-deficient PECs; PTEN loss-induced senescence (PICS) was reported to be a novel type of cellular senescence. Our study reveals that PTEN 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 PTEN-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 PTEN-deficiency induces cellular senescence that restrains tumor progression, as it involves replication stress, strategies promoting PTEN loss-induced senescence are at risk for cancer prevention and therapy. |
