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学科主题: 临床医学
题名:
Alteration of the ATM gene occurs in gastric cancer cell lines and primary tumors associated with cellular response to DNA damage
作者: 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
发表日期: 2004-01-10
DOI: 10.1016/j.mrgentox.2003.09.012
卷: 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
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/66736
Appears in Collections:北京大学临床肿瘤学院_期刊论文

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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

Recommended Citation:
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.
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