Raf kinase inhibitor protein correlates with sensitivity of nasopharyngeal carcinoma to radiotherapy.
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.
Ruan
Lin
L
Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China.
Wang
Guo-Liang
GL
Yi
Hong
H
Chen
Yan
Y
Tang
Can-E
CE
Zhang
Peng-Fei
PF
Li
Mao-Yu
MY
Li
Cui
C
Peng
Fang
F
Li
Jian-Ling
JL
Chen
Zhu-Chu
ZC
Xiao
Zhi-Qiang
ZQ
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
D049488:Phosphatidylethanolamine Binding Protein; D011494:Protein Kinases