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学科主题基础医学
Alpha fetoprotein mediates HBx induced carcinogenesis in the hepatocyte cytoplasm
Zhang, Chao1; Chen, Xiangmei2; Liu, Hui3; Li, Hui1; Jiang, Wei1; Hou, Wenting1; McNutt, Michael A.4; Lu, Fengmin2; Li, Gang1,5
关键词Alpha Fetoprotein Hbv Carcinogenesis Growth Arrest And Dna Damage 45 All Trans Retinoic Acid Nuclear Receptor
刊名INTERNATIONAL JOURNAL OF CANCER
2015-10-15
DOI10.1002/ijc.29548
137期:8页:1818-1829
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Oncology
资助者National Natural Science Foundation of China ; Beijing Natural Science Foundation ; Guangdong Province Natural Science Fund Project ; Shenzhen Research Fund ; National Natural Science Foundation of China ; Beijing Natural Science Foundation ; Guangdong Province Natural Science Fund Project ; Shenzhen Research Fund
研究领域[WOS]Oncology
关键词[WOS]MU-OPIOID RECEPTOR ; GROWTH-INHIBITORY PEPTIDES ; HEPATOCELLULAR-CARCINOMA ; GENE-EXPRESSION ; DNA-REPAIR ; CELLS ; GADD45 ; MECHANISM ; PATHWAY ; PROLIFERATION
英文摘要

Although tumor-associated fetal protein AFP has demonstrated utility as a clinical tumor marker, the significance of intracellular AFP is still unclear. The aim of this study was to explore the role of cytoplasmic AFP during HBx induced carcinogenesis, which had not previously been recognized; 614 HCC patients were analyzed for correlation of HBV infection with AFP level, and much higher AFP levels were found in HBsAg positive patients. Tumor tissue specimens from 20 HCC patients were used for analysis of AFP and GADD45. Analysis of HCC specimens showed that upregulation of cytoplasmic AFP is associated with down-regulation of GADD45 in neoplastic tissue. Transfected HBx promotes transcription of AFP by acting on the elements in the AFP gene regulatory region. HBx itself did not directly impact transcription of GADD45. However, the obstruction of RAR signaling by HBx induced elevation of AFP, which led to down-regulation of GADD45. Cytoplasmic AFP was able to interact with RAR, disrupting its entrance into the nucleus and binding to the elements in the regulatory region of the GADD45 gene. Knockdown of AFP in siRNA-transfected AFP positive cell lines was synchronously associated with an incremental increase of RAR binding to DNA, as well as upregulation of GADD45 and it was contrary in AFP gene-transfected AFP negative cell lines. These results indicate cytoplasmic AFP is not only a histochemical tumor biomarker for human hepatoma but is also an intracellular signal molecule and potential participant in HBx induced hepatocarcinogenesis.

语种英语
所属项目编号81072710 ; 81370522 ; 7101006 ; S2012010010732 ; JCYJ20120616153140835
资助者National Natural Science Foundation of China ; Beijing Natural Science Foundation ; Guangdong Province Natural Science Fund Project ; Shenzhen Research Fund ; National Natural Science Foundation of China ; Beijing Natural Science Foundation ; Guangdong Province Natural Science Fund Project ; Shenzhen Research Fund
WOS记录号WOS:000359350600010
引用统计
被引频次:9[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/400002259/55895
专题基础医学院
作者单位1.Peking Univ, Hlth Sci Ctr, Dept Biochem & Mol Biol, Sch Basic Med Sci, Beijing 100191, Peoples R China
2.Peking Univ, Hlth Sci Ctr, Dept Microbiol, Sch Basic Med Sci, Beijing 100191, Peoples R China
3.Beijing Youan Hosp, Dept Pathol, Beijing, Peoples R China
4.Peking Univ, Hlth Sci Ctr, Dept Pathol, Sch Basic Med Sci, Beijing 100191, Peoples R China
5.Shenzhen PKU HKUST Med Ctr, Shenzhen, Guangdong, Peoples R China
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GB/T 7714
Zhang, Chao,Chen, Xiangmei,Liu, Hui,et al. Alpha fetoprotein mediates HBx induced carcinogenesis in the hepatocyte cytoplasm[J]. INTERNATIONAL JOURNAL OF CANCER,2015,137(8):1818-1829.
APA Zhang, Chao.,Chen, Xiangmei.,Liu, Hui.,Li, Hui.,Jiang, Wei.,...&Li, Gang.(2015).Alpha fetoprotein mediates HBx induced carcinogenesis in the hepatocyte cytoplasm.INTERNATIONAL JOURNAL OF CANCER,137(8),1818-1829.
MLA Zhang, Chao,et al."Alpha fetoprotein mediates HBx induced carcinogenesis in the hepatocyte cytoplasm".INTERNATIONAL JOURNAL OF CANCER 137.8(2015):1818-1829.
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