Overexpression of asparagine synthetase and matrix metalloproteinase 19 confers cisplatin sensitivity in nasopharyngeal carcinoma cells.
Overexpression of asparagine synthetase and matrix metalloproteinase 19 confers cisplatin sensitivity in nasopharyngeal carcinoma cells.
复制标题
DOI：
10.1158/1535-7163.mct-12-1190
复制
发表时间：
2013-10
影响因子：
5.7
通讯作者：
Zhang JT
中科院分区：
文献类型：
--
作者：
Liu RY;Dong Z;Liu J;Zhou L;Huang W;Khoo SK;Zhang Z;Petillo D;Teh BT;Qian CN;Zhang JT
以铂为基础的同步化疗被认为是局部区域晚期鼻咽癌（NPC）的标准治疗方法。然而，与单独放疗相比，只有少数患者从这种治疗方案中受益。鉴定一组预测铂基化疗敏感性的分子标记可能有助于鼻咽癌患者的个性化治疗，以获得更好的临床结果和更小的毒性。此前，我们通过克隆选择从CNE-2细胞中获得顺铂敏感的鼻咽癌细胞系S16，发现eIF3a上调，并通过下调NER蛋白的合成来促进顺铂敏感性。本研究通过基因表达谱分析发现，与CNE-2细胞相比，顺铂敏感的S16细胞中天冬酰胺合成酶（ASNS）、绒毛膜促性腺激素α亚基（CGA）和基质金属蛋白酶19 （MMP19）三个基因表达上调。然而，只有ASNS和MMP19，而不是CGA，通过增强顺铂诱导的DNA损伤和细胞凋亡来促进顺铂敏感性。因此，ASNS和MMP19以及eIF3a是顺铂治疗的敏感性因子，可能作为预测晚期鼻咽癌顺铂敏感性的潜在候选分子标志物。
Platinum-based concurrent chemo-radiotherapy is considered a standard treatment approach for locoregionally advanced nasopharyngeal carcinoma (NPC). However, only a minority of patients benefit from this treatment regimen compared to radiotherapy alone. Identification of a set of molecular markers predicting sensitivity of platinum-based chemotherapy may contribute to personalized treatment of NPC patients for better clinical outcome with less toxicity. Previously, we generated a cisplain sensitive NPC cell line, S16, by clonal selection from CNE-2 cells and found that eIF3a is up-regulated and contributes to cisplatin sensitivity by down-regulating the synthesis of NER proteins. In this study, we conducted a gene expression profiling analysis and found three other genes, asparagine synthetase (ASNS), choriogonadotropin α subunit (CGA), and matrix metalloproteinase 19 (MMP19), that are up-regulated in the cisplatin-sensitive S16 cells compared with the CNE-2 cells. However, only ASNS and MMP19, but not CGA, contributes to cisplatin sensitivity by potentiating cisplatin-induced DNA damage and apoptosis. Thus, ASNS and MMP19, along with eIF3a, are sensitivity factors for cisplatin treatment and may serve as potential candidate molecular markers for predicting cisplatin sensitivity of advanced nasopharyngeal carcinoma.