C-myc上调TCRP1表达与舌癌细胞对顺铂耐受相关

发布时间：2018-05-05 06:00

本文选题：舌癌耐药相关蛋白 + c-myc　；参考：《中国生物化学与分子生物学报》2014年03期

【摘要】：我们先前曾报道了舌癌耐药相关蛋白1(tongue cancer-resistant protein 1,TCRP1)的cDNA克隆,及其在平阳霉素诱导的舌癌耐药细胞系Tca8113/PYM中高表达,而该细胞同时也对顺铂耐受,提示TCRP1可能参与舌癌细胞对顺铂的耐受,但是具体机制目前尚不清楚.本研究证明,TCRP1依赖c-myc的激活机制与舌癌细胞对顺铂耐受相关.生物信息学预测显示,TCRP1启动子存在原癌基因c-myc的结合位点;染色质免疫共沉淀(ChIP)技术证实,c-myc能通过其转录因子结合位点(transcription factor binding site,TFBS)与TCRP1启动子结合;利用半定量RT-PCR、蛋白质免疫印迹和MTS实验检测发现,将c-myc质粒导入舌癌细胞Tca8113中过表达,能显著上调TCRP1的mRNA和蛋白表达水平,且细胞对顺铂的耐受性增强;使用c-myc抑制剂或者siRNA沉默Tca8113/PYM细胞中c-myc,TCRP1的mRNA和蛋白表达水平均下降,且细胞对顺铂的敏感性增强.上述结果提示,转录因子c-myc可与TCRP1基因启动子特异性结合,上调TCRP1的表达,且该基因的表达上调与舌癌细胞对顺铂的耐受相关.
[Abstract]:We have previously reported the cDNA cloning of the drug resistance-associated protein 1(tongue cancer-resistant protein 1 (TCRP1) and its overexpression in pingyangmycin induced tongue cancer cell line Tca8113/PYM, which is also resistant to cisplatin. It suggests that TCRP1 may be involved in cisplatin tolerance in tongue cancer cells, but the mechanism is unclear. This study demonstrated that the activation mechanism of TCRP1 dependent on c-myc was associated with cisplatin tolerance in tongue cancer cells. Bioinformatics prediction showed that TCR P1 promoter had the binding site of proto-oncogene c-myc, and chromatin immunoprecipitation (CP) technique confirmed that c-myc could bind to TCRP1 promoter by transcription of factor binding SiteSs through its transcription factor binding site. By using semi-quantitative RT-PCR, Western blot and MTS assay, it was found that overexpression of c-myc plasmid into Tca8113 of tongue cancer cells could significantly up-regulate the expression of mRNA and protein of TCRP1, and enhance the tolerance of cells to cisplatin. The mRNA and protein expression of c-myctr _ 1 in Tca8113/PYM cells were inhibited by c-myc inhibitor or siRNA, and the sensitivity of the cells to cisplatin was enhanced. These results suggest that the transcription factor c-myc can specifically bind to the promoter of TCRP1 gene and up-regulate the expression of TCRP1, which is related to the tolerance of tongue cancer cells to cisplatin.
【作者单位】：广州医科大学附属肿瘤医院肿瘤研究所;湖南省儿童医院检验科;
【基金】：广东省自然科学基金(No.S2012010008995) 高等学校博士学科点专项科研基金(No.20124423110003)~~
【分类号】：R739.86

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