| | |  | | | | Record from Web of Science® | | | | | | |
| A senescence program controlled by p53 and p16(INK4a) contributes to the outcome of cancer therapy |
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| Author(s): Schmitt CA, Fridman JS, Yang M, Lee S, Baranov E, Hoffman RM, Lowe SW |
| Source: CELL Volume: 109 Issue: 3 Pages: 335-346 Published: MAY 3 2002 |
| Times Cited: 298 References: 41 |
| Abstract: 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. |
| Document Type: Article |
| Language: English |
| Reprint Address: Lowe, SW (reprint author), Cold Spring Harbor Lab, 1 Bungtown Rd, Cold Spring Harbor, NY 11724 USA |
Addresses:
1. Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA
2. AntiCanc Inc, San Diego, CA 92111 USA |
| Publisher: CELL PRESS, 1100 MASSACHUSETTS AVE,, CAMBRIDGE, MA 02138 USA |
| Subject Category: Biochemistry & Molecular Biology; Cell Biology |
| IDS Number: 548WD |
| ISSN: 0092-8674 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |