Identification of BC005512 as a DNA Damage Responsive Murine Endogenous Retrovirus of GLN Family Involved in Cell Growth Regulation
文献类型：期刊论文
| 作者 | Wu, Yuanfeng1; Qi, Xinming1 ; Gong, Likun1; Xing, Guozhen1; Chen, Min1; Miao, Lingling1; Yao, Jun1; Suzuki, Takayoshi2; Furihata, Chie3; Luan, Yang1
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| 刊名 | PLOS ONE
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| 出版日期 | 2012-04-13 |
| 卷号 | 7期号:4 |
| ISSN号 | 1932-6203 |
| DOI | 10.1371/journal.pone.0035010 |
| 文献子类 | Article |
| 英文摘要 | Genotoxicity assessment is of great significance in drug safety evaluation, and microarray is a useful tool widely used to identify genotoxic stress responsive genes. In the present work, by using oligonucleotide microarray in an in vivo model, we identified an unknown gene BC005512 (abbreviated as BC, official full name: cDNA sequence BC005512), whose expression in mouse liver was specifically induced by seven well-known genotoxins (GTXs), but not by non-genotoxins (NGTXs). Bioinformatics revealed that BC was a member of the GLN family of murine endogenous retrovirus (ERV). However, the relationship to genotoxicity and the cellular function of GLN are largely unknown. Using NIH/3T3 cells as an in vitro model system and quantitative real-time PCR, BC expression was specifically induced by another seven GTXs, covering diverse genotoxicity mechanisms. Additionally, dose-response and linear regression analysis showed that expression level of BC in NIH/3T3 cells strongly correlated with DNA damage, measured using the alkaline comet assay,. While in p53 deficient L5178Y cells, GTXs could not induce BC expression. Further functional studies using RNA interference revealed that down-regulation of BC expression induced G1/S phase arrest, inhibited cell proliferation and thus suppressed cell growth in NIH/3T3 cells. Together, our results provide the first evidence that BC005512, a member from GLN family of murine ERV, was responsive to DNA damage and involved in cell growth regulation. These findings could be of great value in genotoxicity predictions and contribute to a deeper understanding of GLN biological functions. |
| WOS关键词 | MUTATION ASSAY ; MOLECULAR-MECHANISMS ; ORGAN VARIATION ; HEPG2 CELLS ; RAT-LIVER ; GENOTOXICITY ; EXPRESSION ; MICE ; CANCER ; P53 |
| 资助项目 | National Natural Science Foundation of China[20807045/B070701] ; National Science and Technology Major Project "Key New Drug Creation and Manufacturing Program", China[2009ZX09301-001] ; National Science and Technology Major Project "Key New Drug Creation and Manufacturing Program", China[2008ZX09305-007] ; National Science and Technology Major Project "Key New Drug Creation and Manufacturing Program", China[2009ZX09501-033] |
| WOS研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:000305341600106 |
| 出版者 | PUBLIC LIBRARY SCIENCE |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278119]  |
| 专题 | 药物安全性评价中心 |
| 通讯作者 | Wu, Yuanfeng |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab New Drug Res, Ctr Drug Safety Evaluat & Res, Shanghai 200031, Peoples R China; 2.Natl Inst Hlth Sci, Div Cellular & Gene Therapy Prod, Tokyo, Japan; 3.Aoyama Gakuin Univ, Sch Sci & Engn, Dept Chem & Biol Sci, Tokyo, Kanagawa 150, Japan |
| 推荐引用方式 GB/T 7714 | Wu, Yuanfeng,Qi, Xinming,Gong, Likun,et al. Identification of BC005512 as a DNA Damage Responsive Murine Endogenous Retrovirus of GLN Family Involved in Cell Growth Regulation[J]. PLOS ONE,2012,7(4). |
| APA | Wu, Yuanfeng.,Qi, Xinming.,Gong, Likun.,Xing, Guozhen.,Chen, Min.,...&Ren, Jin.(2012).Identification of BC005512 as a DNA Damage Responsive Murine Endogenous Retrovirus of GLN Family Involved in Cell Growth Regulation.PLOS ONE,7(4). |
| MLA | Wu, Yuanfeng,et al."Identification of BC005512 as a DNA Damage Responsive Murine Endogenous Retrovirus of GLN Family Involved in Cell Growth Regulation".PLOS ONE 7.4(2012). |
入库方式： OAI收割
来源：上海药物研究所
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