IR@PKUHSC  > 北京大学临床肿瘤学院
学科主题临床医学
Alteration of the ATM gene occurs in gastric cancer cell lines and primary tumors associated with cellular response to DNA damage
Zhang, L; Jia, G; Li, WM; Guo, RF; Cui, JT; Yang, L; Lu, YY
关键词gastric cancer ATM gene mutation cell cycle apoptosis p53 ionizing radiation
刊名MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS
2004-01-10
DOI10.1016/j.mrgentox.2003.09.012
557期:1页:41-51
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Biotechnology & Applied Microbiology ; Genetics & Heredity ; Toxicology
研究领域[WOS]Biotechnology & Applied Microbiology ; Genetics & Heredity ; Toxicology
关键词[WOS]ATAXIA-TELANGIECTASIA GENE ; PERFORMANCE LIQUID-CHROMATOGRAPHY ; DOUBLE-STRAND BREAKS ; IONIZING-RADIATION ; DEPENDENT PHOSPHORYLATION ; CHECKPOINT PATHWAY ; OXIDATIVE STRESS ; NO EVIDENCE ; MUTATIONS ; KINASE
英文摘要

Ataxia telangiectasia mutated (ATM) is the gene mutated in the genetic disorder ataxia telangiectasia (AT), the symptoms of which include sensitivity to radiation and an increased risk of cancer. ATM is a kinase involved in activating the appropriate damage-response pathway, leading to either cell-cycle arrest or apoptosis, and is therefore a key checkpoint molecule in regulating cell-cycle response to DNA damage and responsible for maintenance of genome integrity. However, little is known about the association of ATM mutations with human gastric cancer (HGC). In order to determine the mutation and mRNA expression changes of the ATM gene in HGC, we performed analyses by denaturing high-performance liquid chromatography (DHPLC), DNA sequencing and RT-PCR technique on 13 human gastric tumor cell lines and 30 cases of fresh tumor specimens matched normal tissue. We compared the potential effect of the ATM gene mutation and cell behavior including cell-cycle arrest and induction of apoptosis in the tumor cell lines MGC803 and BGC823 with and without ionizing radiation (IR) exposure. Our data show that frequent variations were observed at 10 exons and 2 cDNA fragments which covered 8 other exons of the ATM gene as 5 out of 13 on the cell lines (38.5%) and 2 out of 30 cases in the tissue specimens (6.7%). All point mutations were confirmed as base substitutions (5982T-C; 6620A-G; 8684G-G/A; 9389C-G) and deletions (1079delC) by use of DNA sequencing. Among the mutations, one was reported previously in breast cancer, the other five have not yet been reported. The expression of ATM was significantly lower in five cell lines (MGC803; MKN45; SGC7901; GES and SUN-1)than in two others (BGC823 and RF48). G2/M cell-cycle arrest and apoptosis were observed in ATM-deficient MGC803 cells challenged with IR. A transient up-regulation of p53 occurred I h post-IR in BGC823 cells but not in MGC803 cells. Our findings suggest that ATM mutations might be a pathogenic factor for an increased risk of gastric cancer, and the dysfunction of ATM may lead to a hypersensitivity to ionizing radiation in gastric cancer cells, possibly by a p53-dependent pathway. (C) 2003 Elsevier B.V. All fights reserved.

语种英语
WOS记录号WOS:000188530700005
引用统计
被引频次:18[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/66736
专题北京大学临床肿瘤学院
作者单位1.Peking Univ, Beijing Inst Canc Res, Sch Oncol, Beijing Mol Oncol Lab, Beijing 100034, Peoples R China
2.Peking Univ, Sch Publ Hlth, Beijing 100083, Peoples R China
推荐引用方式
GB/T 7714
Zhang, L,Jia, G,Li, WM,et al. Alteration of the ATM gene occurs in gastric cancer cell lines and primary tumors associated with cellular response to DNA damage[J]. MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS,2004,557(1):41-51.
APA Zhang, L.,Jia, G.,Li, WM.,Guo, RF.,Cui, JT.,...&Lu, YY.(2004).Alteration of the ATM gene occurs in gastric cancer cell lines and primary tumors associated with cellular response to DNA damage.MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS,557(1),41-51.
MLA Zhang, L,et al."Alteration of the ATM gene occurs in gastric cancer cell lines and primary tumors associated with cellular response to DNA damage".MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS 557.1(2004):41-51.
条目包含的文件
条目无相关文件。
个性服务
推荐该条目
保存到收藏夹
查看访问统计
导出为Endnote文件
谷歌学术
谷歌学术中相似的文章
[Zhang, L]的文章
[Jia, G]的文章
[Li, WM]的文章
百度学术
百度学术中相似的文章
[Zhang, L]的文章
[Jia, G]的文章
[Li, WM]的文章
必应学术
必应学术中相似的文章
[Zhang, L]的文章
[Jia, G]的文章
[Li, WM]的文章
相关权益政策
暂无数据
收藏/分享
所有评论 (0)
暂无评论
 

除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。