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http://ir.nhri.org.tw/handle/3990099045/8206
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| Title: | Chronic treatment with cisplatin induces replication-dependent sister chromatid recombination to confer cisplatin-resistant phenotype in nasopharyngeal carcinoma |
| Authors: | Su, WP;Hsu, SH;Wu, CK;Chang, SB;Lin, YJ;Yang, WB;Hung, JJ;Chiu, WT;Tzeng, SF;Tseng, YL;Chang, JY;Su, WC;Liaw, H |
| Contributors: | National Institute of Cancer Research |
| Abstract: | Cisplatin can cause intrastrand and interstrand crosslinks between purine bases and is a chemotherapeutic drug widely used to treat cancer. However, the major barrier to the efficacy of the treatment is drug resistance. Homologous recombination (HR) plays a central role in restoring stalled forks caused by DNA lesions. Here, we report that chronic treatment with cisplatin induces HR to confer cisplatin resistance in nasopharyngeal carcinoma (NPC) cells. A high frequency of sister chromatid exchanges (SCE) occurs in the cisplatin-resistant NPC cells. In addition, several genes in the Fanconi anemia (FA) and template switching (TS) pathways show elevated expression. Significantly, depletion of HR gene BRCA1, TS gene UBC13, or FA gene FANCD2 suppresses SCE and causes cells to accumulate in the S phase, concomitantly with high gammaH2AX foci formation in the presence of low-dose cisplatin. Consistent with this result, depletion of several genes in the HR, TS, or FA pathway sensitizes the cisplatin-resistant NPC cells to cisplatin. Our results suggest that the enhanced HR, in coordination with the FA and TS pathways, underlies the cisplatin resistance. Targeting the HR, TS, or FA pathways could be a potential therapeutic strategy for treating cisplatin-resistant cancer. |
| Date: | 2014-08 |
| Relation: | Oncotarget. 2014 Aug;5(15):6323-6337. |
| Link to: | http://dx.doi.org/10.18632/oncotarget.2210 |
| Cited Times(WOS): | https://www.webofscience.com/wos/woscc/full-record/WOS:000347919500038 |
| Cited Times(Scopus): | http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84906330203 |
| Appears in Collections: | [張俊彥] 期刊論文
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| PUB25051366.pdf | | 3594Kb | Adobe PDF | 424 | View/Open |
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