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学科主题: 基础医学
题名:
Alpha fetoprotein mediates HBx induced carcinogenesis in the hepatocyte cytoplasm
作者: 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
发表日期: 2015-10-15
DOI: 10.1002/ijc.29548
卷: 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
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
项目资助者: 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
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内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/55895
Appears in Collections:基础医学院_期刊论文

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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

Recommended Citation:
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.
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