| First Author | Palacio L | Year | 2017 |
| Journal | Oncogene | Volume | 36 |
| Issue | 9 | Pages | 1309-1314 |
| PubMed ID | 27568978 | Mgi Jnum | J:236390 |
| Mgi Id | MGI:5806001 | Doi | 10.1038/onc.2016.298 |
| Citation | Palacio L, et al. (2017) Sustained p16(INK4a) expression is required to prevent IR-induced tumorigenesis in mice. Oncogene 36(9):1309-1314 |
| abstractText | Exposure of murine and human tissues to ionizing radiation (IR) induces the expression of p16(INK4a), a tumor suppressor gene and senescence/aging biomarker. Increased p16(INK4a) expression is often delayed several weeks post exposure to IR. In this context, it remains unclear if it occurs to suppress aberrant cellular growth of potentially transformed cells or is simply a result of IR-induced loss of tissue homeostasis. To address this question, we used a conditional p16(INK4a) null mouse model and determined the impact of p16(INK4a) inactivation long-term post exposure to IR. We found that, in vitro, bone marrow stromal cells exposed to IR enter DNA replication following p16(INK4a) inactivation. However, these cells did not resume growth; instead, they mostly underwent cell cycle arrest in G2. Similarly, delayed inactivation of p16(INK4a) in mice several weeks post exposure to IR resulted in increased BrdU incorporation and cancer incidence. In fact, we found that the onset of tumorigenesis was similar whether p16(INK4a) was inactivated before or after exposure to IR. Overall, our results suggest that IR-induced p16(INK4a) dependent growth arrest is reversible in mice and that sustained p16(INK4a) expression is necessary to protect against tumorigenesis. |
