title: Raf kinase inhibitor protein correlates with sensitivity of nasopharyngeal carcinoma to radiotherapy.
abstract: Raf kinase inhibitory protein (RKIP) is a metastasis suppressor whose expression is reduced in nasopharyngeal carcinoma (NPC) tissues and is absent in NPC metastases. To investigate the effect of RKIP on radiosensitivity of NPC, high metastatic 5-8F with low RKIP expression and non-metastatic 6-10B with high RKIP expression were stably transfected with plasmids that expressed sense and antisense RKIP cDNA. Overexpression of RKIP sensitized 5-8F cells to radiation-induced cell death, G(2)-M cell cycle arrest and apoptosis. In contrast, downexpression of RKIP in 6-10B cells protected cells from radiation-induced cell death, G(2)-M cell cycle arrest and apoptosis. In addition, RKIP expression altered the radiosensitivity of NPC cells through MEK and ERK phosphorylation changes of Raf-1/MEK/ERK signaling pathway. We further investigated the RKIP expression in NPC patients and its association with patients' survival after radiotherapy. Downexpression of RKIP was significantly correlated with advanced clinical stage, lymph node metastasis and radioresistance. Furthermore, survival curves showed that patients with RKIP downexpression had a poor prognosis and induced relapse. Multivariate analysis confirmed that RKIP expression was an independent prognostic indicator. The data suggested that RKIP was a potential biomarker for the radiosensitivity and prognosis of NPC, and its dysregulation might play an important role in the radioresistance of NPC.
authors.affiliation: Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Ruan
authors.forename: Guo-Liang
authors.initials: GL
authors.lastname: Wang
authors.forename: Hong
authors.initials: H
authors.lastname: Yi
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.forename: Can-E
authors.initials: CE
authors.lastname: Tang
authors.forename: Peng-Fei
authors.initials: PF
authors.lastname: Zhang
authors.forename: Mao-Yu
authors.initials: MY
authors.lastname: Li
authors.forename: Cui
authors.initials: C
authors.lastname: Li
authors.forename: Fang
authors.initials: F
authors.lastname: Peng
authors.forename: Jian-Ling
authors.initials: JL
authors.lastname: Li
authors.forename: Zhu-Chu
authors.initials: ZC
authors.lastname: Chen
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Xiao
mesh_terms: D017209:Apoptosis; D015153:Blotting, Western; D002453:Cell Cycle; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D006801:Humans; D009303:Nasopharyngeal Neoplasms / Q000473:pathology / Q000503:physiopathology / Q000532:radiotherapy*; D049488:Phosphatidylethanolamine Binding Protein / Q000502:physiology*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D011836:Radiation Tolerance
chemical_list: D049488:Phosphatidylethanolamine Binding Protein; D011494:Protein Kinases