Identification of chemoresistant factors by protein expression analysis with iTRAQ for head and neck carcinoma.
Identification of chemoresistant factors by protein expression analysis with iTRAQ for head and neck carcinoma.
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DOI：
10.1038/bjc.2014.395
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发表时间：
2014-08-12
影响因子：
8.8
通讯作者：
Ogawa, T.
中科院分区：
文献类型：
--
作者：
Nishimura, K.;Tsuchiya, Y.;Okamoto, H.;Ijichi, K.;Gosho, M.;Fukayama, M.;Yoshikawa, K.;Ueda, H.;Bradford, C. R.;Carey, T. E.;Ogawa, T.
关键词：
顺铂和其他抗癌药物在头颈部鳞状细胞癌的治疗中很重要;然而，一些肿瘤会产生耐药性。如果能够在治疗前确定耐药性，就可以避免不必要的药物给药。在这里，我们研究了化学耐药的因素，在蛋白质水平上进行综合分析。使用了四种人癌细胞系：顺铂敏感的UM-SCC-23、具有获得性顺铂耐药的UM-SCC-23-CDDPR、天然顺铂耐药的UM-SCC-81 B和具有获得性5-氟尿嘧啶耐药的UM-SCC-23/WR。用iTRAQ标记提取的蛋白质，并通过串联质谱法进行分析以鉴定耐药性。通过蛋白质印迹法确认蛋白质表达，并使用siRNA进行功能分析。共鉴定出13种多药耐药蛋白，以及7种对顺铂具有特异性耐药的蛋白，包括α-烯醇化酶。这些蛋白质在顺铂耐药和敏感细胞系中的差异表达通过蛋白质印迹法证实。siRNA对α-烯醇化酶的功能分析显示，UM-SCC-81 B细胞对顺铂的敏感性显著增加，UM-SCC-23-CDDPR细胞对顺铂的敏感性略有增加，而UM-SCC-23/WR细胞对顺铂的敏感性无明显变化。我们使用最新的蛋白质组技术鉴定了被认为介导抗癌药物耐药性的蛋白质，并将α-烯醇化酶鉴定为真正的顺铂耐药因子。这些蛋白质可用作抗癌剂抗性的生物标志物和癌症治疗的靶点。
Cisplatin and other anticancer drugs are important in the treatment of head and neck squamous cell carcinoma; however, some tumours develop drug resistance. If chemoresistance could be determined before treatment, unnecessary drug administration would be avoided. Here, we investigated chemoresistance factors by comprehensive analyses at the protein level. Four human carcinoma cell lines were used: cisplatin-sensitive UM-SCC-23, UM-SCC-23-CDDPR with acquired cisplatin resistance, naturally cisplatin-resistant UM-SCC-81B, and UM-SCC-23/WR with acquired 5-fluorouracil resistance. Extracted proteins were labelled with iTRAQ and analysed by tandem mass spectrometry to identify resistance. Protein expression was confirmed by western blotting and functional analysis was carried out using siRNA. Thirteen multiple-drug resistance proteins were identified, as well as seven proteins with specific resistance to cisplatin, including α-enolase. Differential expression of these proteins in cisplatin-resistant and -sensitive cell lines was confirmed by western blotting. Functional analysis for α-enolase by siRNA showed that cisplatin sensitivity significantly was increased in UM-SCC-81B and slightly in UM-SCC-23-CDDPR but not in UM-SCC-23/WR cells. We identified proteins thought to mediate anticancer drug resistance using recent proteome technology and identified α-enolase as a true cisplatin chemoresistance factor. Such proteins could be used as biomarkers for anticancer agent resistance and as targets of cancer therapy.
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影响因子：
5.3
作者：
Hsu, Kai-Wen;Hsieh, Rong-Hong;Yeh, Tien-Shun
通讯作者：
Yeh, Tien-Shun
影响因子：
254.7
作者：
BORING, CC;SQUIRES, TS;TONG, T
通讯作者：
TONG, T
DOI：
10.1002/hed.21198
发表时间：
2010-04
影响因子：
2.9
作者：
Brenner, J. Chad;Graham, Martin P.;Kumar, Bhavna;Saunders, Lindsay M.;Kupfer, Robbi;Lyons, Robert H.;Bradford, Carol R.;Carey, Thomas E.
通讯作者：
Carey, Thomas E.
影响因子：
4.8
作者：
Craft, George E.;Chen, Anshu;Nairn, Angus C.
通讯作者：
Nairn, Angus C.
影响因子：
28.2
作者：
Pickering CR;Zhang J;Yoo SY;Bengtsson L;Moorthy S;Neskey DM;Zhao M;Ortega Alves MV;Chang K;Drummond J;Cortez E;Xie TX;Zhang D;Chung W;Issa JP;Zweidler-McKay PA;Wu X;El-Naggar AK;Weinstein JN;Wang J;Muzny DM;Gibbs RA;Wheeler DA;Myers JN;Frederick MJ
通讯作者：
Frederick MJ