Identification of chemoresistant factors by protein expression analysis with iTRAQ for head and neck carcinoma View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-07-17

AUTHORS

K Nishimura, Y Tsuchiya, H Okamoto, K Ijichi, M Gosho, M Fukayama, K Yoshikawa, H Ueda, C R Bradford, T E Carey, T Ogawa

ABSTRACT

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. More... »

PAGES

799-806

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/bjc.2014.395

DOI

http://dx.doi.org/10.1038/bjc.2014.395

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1025500214

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/25032734


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29 schema:description BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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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37 Extracted proteins
38 UM
39 UM-SCC
40 UM-SCC-23
41 UM-SCC-23/WR
42 UM-SCC-23/WR cells
43 WR
44 WR cells
45 Western blotting
46 administration
47 agent resistance
48 analysis
49 anticancer agent resistance
50 anticancer drug resistance
51 anticancer drugs
52 biomarkers
53 blotting
54 cancer therapy
55 carcinoma
56 carcinoma cell lines
57 cell carcinoma
58 cell lines
59 cells
60 chemoresistance
61 chemoresistance factor
62 chemoresistant factors
63 cisplatin
64 cisplatin chemoresistance factor
65 cisplatin resistance
66 cisplatin sensitivity
67 cisplatin-resistant UM-SCC
68 cisplatin-sensitive UM-SCC-23
69 comprehensive analysis
70 differential expression
71 drug resistance
72 drugs
73 enolase
74 expression
75 expression analysis
76 factors
77 functional analysis
78 head
79 human carcinoma cell lines
80 iTRAQ
81 identification
82 levels
83 lines
84 mass spectrometry
85 multiple drug resistance proteins
86 neck carcinoma
87 neck squamous cell carcinoma
88 protein
89 protein expression
90 protein expression analysis
91 protein levels
92 proteome technology
93 recent proteome technology
94 resistance
95 resistance protein
96 sensitive cell lines
97 sensitivity
98 siRNA
99 specific resistance
100 spectrometry
101 squamous cell carcinoma
102 such proteins
103 tandem mass spectrometry
104 target
105 technology
106 therapy
107 treatment
108 treatment of head
109 true cisplatin chemoresistance factor
110 tumors
111 unnecessary drug administration
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