| First Author | Schmitt CA | Year | 2002 |
| Journal | Cell | Volume | 109 |
| Issue | 3 | Pages | 335-46 |
| PubMed ID | 12015983 | Mgi Jnum | J:76474 |
| Mgi Id | MGI:2179564 | Doi | 10.1016/s0092-8674(02)00734-1 |
| Citation | Schmitt CA, et al. (2002) A senescence program controlled by p53 and p16INK4a contributes to the outcome of cancer therapy. Cell 109(3):335-46 |
| abstractText | p53 and INK4a/ARF mutations promote tumorigenesis and drug resistance, in part, by disabling apoptosis. We show that primary murine lymphomas also respond to chemotherapy by engaging a senescence program controlled by p53 and p16(INK4a). Hence, tumors with p53 or INK4a/ARF mutations-but not those lacking ARF alone-respond poorly to cyclophosphamide therapy in vivo. Moreover, tumors harboring a Bcl2-mediated apoptotic block undergo a drug-induced cytostasis involving the accumulation of p53, p16(INK4a), and senescence markers, and typically acquire p53 or INK4a mutations upon progression to a terminal stage. Finally, mice bearing tumors capable of drug-induced senescence have a much better prognosis following chemotherapy than those harboring tumors with senescence defects. Therefore, cellular senescence contributes to treatment outcome in vivo. |
