Identification of radiation-specific responses from gene expression profile

被引:95
作者
Park, WY
Hwang, CI
Im, CN
Kang, MJ
Woo, JH
Kim, JH
Kim, YS
Kim, JH
Kim, H
Kim, KA
Yu, HJ
Lee, SJ
Lee, YS
Seo, JS
机构
[1] Seoul Natl Univ, Coll Med, Dept Biochem & Mol Biol, Chongnogu, Seoul 110799, South Korea
[2] Seoul Natl Univ, Ilchun Mol Med Inst, Seoul, South Korea
[3] Seoul Natl Univ, Dept Internal Med, Seoul, South Korea
[4] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul, South Korea
[5] Seoul Natl Univ, Grad Sch Publ Hlth, Dept Biostat, Seoul, South Korea
[6] Macrogen Inc, Seoul, South Korea
[7] Korea Canc Ctr Hosp, Lab Radiat Effect, Seoul, South Korea
关键词
gamma-irradiation; cDNA microarray; p53; cytoplasmic epoxide hydrolase; phospholipase C gamma 2;
D O I
10.1038/sj.onc.1205977
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The responses to ionizing radiation (IR) in tumors are dependent on cellular context. We investigated radiation-related expression patterns in Jurkat T cells with nonsense mutation in p53 using cDNA microarray. Expression of 2400 genes in gamma-irradiated cells was distinct from other stimulations like anti-CD3, phetohemagglutinin (PHA) and concanavalin A (ConA) in unsupervised clustering analysis. Among them, 384 genes were selected for their IR-specific changes to make 'RadChip'. In spite of p53 status, every type of cells showed similar patterns in expression of these genes upon gamma-radiation. Moreover, radiation-induced responses were clearly separated from the responses to other genotoxic stress like UV radiation, cisplatin and doxorubicin. We focused on two IR-related genes, phospholipase Cgamma2 (PLCG2) and cytosolic epoxide hydrolase (EPHX2), which were increased at 12 h after gamma-radiation in RT-PCR. TPCK could suppress the induction of these two genes in either of Jurkat T cells and PBMCs, which might suggest the transcriptional regulation of PLCG2 and EPHX2 by NF-gammaB upon gamma-radiation. From these results, we could identify the IR-specific genes from expression profiling, which can be used as radiation biomarkers to screen radiation exposure as well as probing the mechanism of cellular responses to ionizing radiation.
引用
收藏
页码:8521 / 8528
页数:8
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