Alpha fetoprotein mediates HBx induced carcinogenesis in the hepatocyte cytoplasm.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read More Add to Saved list
  • Additional Information
    • Source:
      Publisher: Wiley-Liss Country of Publication: United States NLM ID: 0042124 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1097-0215 (Electronic) Linking ISSN: 00207136 NLM ISO Abbreviation: Int J Cancer Subsets: MEDLINE
    • Publication Information:
      Publication: 1995- : New York, NY : Wiley-Liss
      Original Publication: 1966-1984 : Genève : International Union Against Cancer
    • Subject Terms:
      Cell Transformation, Viral*; Carcinoma, Hepatocellular/*virology ; Cell Cycle Proteins/*metabolism ; Hepatitis B virus/*physiology ; Liver Neoplasms/*virology ; Nuclear Proteins/*metabolism ; alpha-Fetoproteins/*metabolism; Carcinoma, Hepatocellular/genetics ; Carcinoma, Hepatocellular/metabolism ; Cell Cycle Proteins/genetics ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; HEK293 Cells ; HeLa Cells ; Hep G2 Cells ; Humans ; Liver Neoplasms/genetics ; Liver Neoplasms/metabolism ; Nuclear Proteins/genetics ; Receptors, Retinoic Acid/genetics ; Receptors, Retinoic Acid/metabolism ; Retrospective Studies ; alpha-Fetoproteins/genetics
    • Abstract:
      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 GADD45α. Analysis of HCC specimens showed that upregulation of cytoplasmic AFP is associated with down-regulation of GADD45α 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 GADD45α. However, the obstruction of RAR signaling by HBx induced elevation of AFP, which led to down-regulation of GADD45α. 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 GADD45α 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 GADD45α 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.
      (© 2015 UICC.)
    • Contributed Indexing:
      Keywords: HBV; all trans retinoic acid; alpha fetoprotein; carcinogenesis; growth arrest and DNA damage 45α; nuclear receptor
    • Accession Number:
      0 (AFP protein, human)
      0 (Cell Cycle Proteins)
      0 (GADD45A protein, human)
      0 (Nuclear Proteins)
      0 (Receptors, Retinoic Acid)
      0 (alpha-Fetoproteins)
    • Publication Date:
      Date Created: 20150408 Date Completed: 20151124 Latest Revision: 20160303
    • Publication Date:
      20240829
    • Accession Number:
      10.1002/ijc.29548
    • Accession Number:
      25846475