title: Identification Keratin 1 as a cDDP-resistant protein in nasopharyngeal carcinoma cell lines.
abstract: Multidrug resistance (MDR) to anticancer drugs is a major obstacle to successful chemotherapy of tumors. Understanding the molecular basis to chemoresistance is likely to provide better treatment. Cell lines resistant to cis-diamminedichloroplatinum (CNE2/cDDP) were established from human nasopharyngeal carcinoma (NPC) cell lines CNE2. Comparative proteomics involving 2-dimensional gel electrophoresis (2-DE) and ESI-Q-TOF-MS were performed on protein extracted from CNE2 and CNE2/cDDP cell lines to screen drug resistance-related proteins. Keratin 1 (KRT1), cathepsin D (CTSD) and annexin a5 (ANXA5) were identified as three proteins showing higher expression in CNE2/cDDP compared to CNE2. Furthermore, suppression of KRT1 expression by siRNA resulted in decreased MDR in siRNA-CNE2/cDDP cells. And upregulation of KRT1 could result in increased of drug resistance in NPC cell lines. Taken together, KRT1 protein and its activity levels were higher in cDDP-resistant NPC cell lines compared to their parental cell lines. These data clearly linked KRT1 and cDDP resistance mechanisms. KRT1 could serve as a biomarker for chemotherapy sensitivity of NPC.
authors.affiliation: Department of Oncology, Xiangya Hospital, Central South University, Changsha 410008, P. R. China.
authors.forename: Sanyuan
authors.initials: S
authors.lastname: Tang
authors.forename: Weiguo
authors.initials: W
authors.lastname: Huang
authors.forename: Meizuo
authors.initials: M
authors.lastname: Zhong
authors.forename: Leilan
authors.initials: L
authors.lastname: Yin
authors.forename: Hao
authors.initials: H
authors.lastname: Jiang
authors.forename: Suping
authors.initials: S
authors.lastname: Hou
authors.forename: Pingping
authors.initials: P
authors.lastname: Gan
authors.forename: Yujuan
authors.initials: Y
authors.lastname: Yuan
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D002277:Carcinoma; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical; D019008:Drug Resistance, Neoplasm / Q000235:genetics / Q000502:physiology; D015180:Electrophoresis, Gel, Two-Dimensional; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D053556:Keratin-1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D013058:Mass Spectrometry; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000494:pharmacology; D014162:Transfection; D054928:Validation Studies as Topic
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C491616:KRT1 protein, human; D053556:Keratin-1; D034741:RNA, Small Interfering; D002945:Cisplatin