机构：[1]J. B. Mitchell E. Y. Chuang Radiation Biology and Oncology Branches, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA[2]Department of Gastroenterology and Hepatology, The Fourth Hospital, Hebei Medical University, Shijiazhuang, China河北医科大学第四医院免疫风湿科临床科室[3]Institute of biotechnology, College of Bio-Resources and Agriculture, National Taiwan University, Taipei, Taiwan[4]Laboratory of Comparative Carcinogenesis, National Cancer Institute at Frederick, National Institutes of Health, Frederick, MD 21702, USA[5]Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, No. 1 Section 4 Roosevelt Road, Taipei, Taiwan[6]Departments of Electrical Engineering and Life Science, Graduate Institute of Epidemiology, National Taiwan University, Taipei, Taiwan[7]Research Center For Medical Excellence, National Taiwan University, Taipei, Taiwan[8]Division of Neurosciences, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA[9]Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, MA 02115, USA
In cancer, gene silencing via hypermethylation is as common as genetic mutations in p53. Understanding the relationship between mutant p53 and hypermethylation of other tumor suppressor genes is essential when elucidate mechanisms of tumor development. In this study, two isogenic human B lymphoblast cell lines with different p53 status include TK6 containing wild-type p53 and WTK1 with mutant p53 were used and contrasted. Lower levels of p16(ink4A) protein were detected in WTK1 cells than in TK6 cells, which were accompanied by increased DNA (cytosine-5)-methyltransferase 1 (DNMT1) gene expression as well as hypermethylation of the p16(ink4A) promoter. siRNA experiments to transiently knock down wild-type p53 in TK6 cells resulted in increase of DNMT1 expression as well as decrease of p16(ink4A) protein. Conversely, siRNA knockdown of mutant p53 in WTK1 cells did not alter either DNMT1 or p16(ink4A) protein levels. Furthermore, loss of suppression function of mutant p53 to DNMT1 in WTK1 was caused by the attenuation of its binding ability to the DNMT1 promoter. In summary, we provide evidences to elucidate the relationship between mutant p53 and DNMT1. Our results indicate that mutant p53 loses its ability to suppress DNMT1 expression, and thus enhances methylation levels of the p16(ink4A) promoter and subsequently down-regulates p16(ink4A) protein.
基金：
DIVISION OF BASIC SCIENCES - NCIUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [Z01BC010544, Z01BC010544, Z01BC010544] Funding Source: NIH RePORTER; DIVISION OF CLINICAL SCIENCES - NCIUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [Z01SC006387, Z01SC006387, Z01SC006387, Z01SC006321, Z01SC006321, Z01SC006321, Z01SC006387, Z01SC006321, Z01SC006387, Z01SC006387, Z01SC006387, Z01SC006387, Z01SC006321, Z01SC006321, Z01SC006387, Z01SC006321, Z01SC006321, Z01SC006321, Z01SC006321, Z01SC006387, Z01SC006321, Z01SC006387] Funding Source: NIH RePORTER; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [ZIASC006321, Z01BC010544, ZIASC006321, ZIASC006321, ZIASC006321, ZIASC006387, Z01SC006321, ZIASC006321, ZIASC006387, ZIASC006321, ZIASC006321, ZIASC006387, ZIASC006387, ZIASC006387, ZIABC010544, ZIASC006387, ZIASC006321, ZIABC010544, ZIASC006321, ZIASC006387, ZIASC006321, Z01SC006321, Z01SC006387, ZIASC006387, ZIASC006387, ZIASC006387, Z01SC006387, Z01BC010544] Funding Source: NIH RePORTER; Intramural NIH HHSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA Funding Source: Medline
第一作者机构：[1]J. B. Mitchell E. Y. Chuang Radiation Biology and Oncology Branches, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA[2]Department of Gastroenterology and Hepatology, The Fourth Hospital, Hebei Medical University, Shijiazhuang, China
共同第一作者：
通讯作者：
通讯机构：[1]J. B. Mitchell E. Y. Chuang Radiation Biology and Oncology Branches, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA[5]Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, No. 1 Section 4 Roosevelt Road, Taipei, Taiwan[6]Departments of Electrical Engineering and Life Science, Graduate Institute of Epidemiology, National Taiwan University, Taipei, Taiwan[7]Research Center For Medical Excellence, National Taiwan University, Taipei, Taiwan
推荐引用方式(GB/T 7714)：
Guo Zhanjun,Tsai Mong-Hsun,Shiao Yih-Horng,et al.DNA (cytosine-5)-methyltransferase 1 as a mediator of mutant p53-determined p16(ink4A) down-regulation[J].JOURNAL OF BIOMEDICAL SCIENCE.2008,15(2):163-168.doi:10.1007/s11373-007-9222-y.
APA：
Guo, Zhanjun,Tsai, Mong-Hsun,Shiao, Yih-Horng,Chen, Li-Han,Wei, Mei-Ling...&Chuang, Eric Y..(2008).DNA (cytosine-5)-methyltransferase 1 as a mediator of mutant p53-determined p16(ink4A) down-regulation.JOURNAL OF BIOMEDICAL SCIENCE,15,(2)
MLA：
Guo, Zhanjun,et al."DNA (cytosine-5)-methyltransferase 1 as a mediator of mutant p53-determined p16(ink4A) down-regulation".JOURNAL OF BIOMEDICAL SCIENCE 15..2(2008):163-168
医学