Mechanisms of increased risk of tumorigenesis in Atm and Brca1 double heterozygosity
文献类型：期刊论文
| 作者 | Wang, Jufang2 ; Su, Fengtao2; Smilenov, Lubomir B.3; Zhou, Libin2; Hu, Wentao1,2; Ding, Nan1,2; Zhou, Guangming2
|
| 刊名 | RADIATION ONCOLOGY
 |
| 出版日期 | 2011-08-17 |
| 卷号 | 6期号:1页码:8 |
| 关键词 | heterozygosity haploinsufficiency tumorigenesis DNA damage cell cycle checkpoint genomic instability |
| ISSN号 | 1748-717X |
| DOI | 10.1186/1748-717X-6-96 |
| 英文摘要 | Background: Both epidemiological and experimental studies suggest that heterozygosity for a single gene is linked with tumorigenesis and heterozygosity for two genes increases the risk of tumor incidence. Our previous work has demonstrated that Atm/Brca1 double heterozygosity leads to higher cell transformation rate than single heterozygosity. However, the underlying mechanisms have not been fully understood yet. In the present study, a series of pathways were investigated to clarify the possible mechanisms of increased risk of tumorigenesis in Atm and Brca1 heterozygosity. Methods: Wild type cells, Atm or Brca1 single heterozygous cells, and Atm/Brca1 double heterozygous cells were used to investigate DNA damage and repair, cell cycle, micronuclei, and cell transformation after photon irradiation. Results: Remarkable high transformation frequency was confirmed in Atm/Brca1 double heterozygous cells compared to wild type cells. It was observed that delayed DNA damage recognition, disturbed cell cycle checkpoint, incomplete DNA repair, and increased genomic instability were involved in the biological networks. Haploinsufficiency of either ATM or BRCA1 negatively impacts these pathways. Conclusions: The quantity of critical proteins such as ATM and BRCA1 plays an important role in determination of the fate of cells exposed to ionizing radiation and double heterozygosity increases the risk of tumorigenesis. These findings also benefit understanding of the individual susceptibility to tumor initiation. |
| WOS关键词 | DOUBLE-STRAND BREAKS ; DNA-DAMAGE RESPONSE ; ATAXIA-TELANGIECTASIA ; IONIZING-RADIATION ; WILD-TYPE ; X-RAY ; HOMOLOGOUS RECOMBINATION ; INCREASED SENSITIVITY ; CELL-TRANSFORMATION ; CANCER RISK |
| 资助项目 | Major State Basic Research Development Program of China (973 Program)[2010CB834201] ; Chinese Academy of Sciences[0760140BR0] ; US Department of Energy[DE-FG02-03ER63629] ; NASA[NAG 9-1519] ; Project 5[PO1-CA97403] |
| WOS研究方向 | Oncology ; Radiology, Nuclear Medicine & Medical Imaging |
| 语种 | 英语 |
| WOS记录号 | WOS:000294681700001 |
| 出版者 | BIOMED CENTRAL LTD |
| 资助机构 | Major State Basic Research Development Program of China (973 Program) ; Chinese Academy of Sciences ; US Department of Energy ; NASA ; Project 5 |
| 源URL | [http://119.78.100.186/handle/113462/24457]  |
| 专题 | 中国科学院近代物理研究所 |
| 通讯作者 | Zhou, Guangming |
| 作者单位 | 1.Chinese Acad Sci, Grad Sch, Beijing 100049, Peoples R China 2.Chinese Acad Sci, Key Lab Heavy Ion Radiat Biol & Med, Inst Modern Phys, Lanzhou 730000, Peoples R China 3.Columbia Univ, Ctr Radiol Res, Med Ctr, New York, NY 10032 USA |
| 推荐引用方式 GB/T 7714 | Wang, Jufang,Su, Fengtao,Smilenov, Lubomir B.,et al. Mechanisms of increased risk of tumorigenesis in Atm and Brca1 double heterozygosity[J]. RADIATION ONCOLOGY,2011,6(1):8. |
| APA | Wang, Jufang.,Su, Fengtao.,Smilenov, Lubomir B..,Zhou, Libin.,Hu, Wentao.,...&Zhou, Guangming.(2011).Mechanisms of increased risk of tumorigenesis in Atm and Brca1 double heterozygosity.RADIATION ONCOLOGY,6(1),8. |
| MLA | Wang, Jufang,et al."Mechanisms of increased risk of tumorigenesis in Atm and Brca1 double heterozygosity".RADIATION ONCOLOGY 6.1(2011):8. |
入库方式： OAI收割
来源：近代物理研究所
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