| First Author | Kim Y | Year | 2005 |
| Journal | Oncogene | Volume | 24 |
| Issue | 3 | Pages | 407-18 |
| PubMed ID | 15543230 | Mgi Jnum | J:95514 |
| Mgi Id | MGI:3526462 | Doi | 10.1038/sj.onc.1208222 |
| Citation | Kim Y, et al. (2005) p12(CDK2-AP1) mediates DNA damage responses induced by cisplatin. Oncogene 24(3):407-18 |
| abstractText | We examined the biological role of p12(CDK2-AP1) in cisplatin-mediated responses by using murine ES p12(CDK2-AP1) knockout clones generated by a targeted disruption of murine p12(CDK2-AP1). Homozygous knockout clones showed an increased cellular proliferation along with an increase in S and a decrease in G2/M phase populations. Interestingly, ES p12(CDK2-AP1) knockout clones showed a resistance to cisplatin treatment along with an increased DNA repair activity assessed by host cell reactivation assay using a cisplatin-damaged reporter DNA and a significant reduction of apoptosis upon cisplatin treatment. By using stable p12(CDK2-AP1) short interfering RNA (siRNA) clones from human normal oral keratinocytes, we confirmed that downregulation of p12(CDK2-AP1) resulted in a resistance to cisplatin. More interestingly, cisplatin treatment resulted in a reduction of CDK2 kinase activity in control clones, but p12(CDK2-AP1) knockout clones showed a sustained CDK2 kinase activity. These data suggest that p12(CDK2-AP1) plays a role in cisplatin-mediated cellular responses by modulating CDK2 activity. These data further suggest p12(CDK2-AP1) is a potential gene therapeutic agent for oral/head and neck cancer in conjunction with DNA-damaging agents such as cisplatin. |
