Research article summary (published 13 Oct 2009):

Increased expression of ErbB-2 in liver is associated with hepatitis B x antigen and shorter survival in patients with liver cancer.

Full Abstract

Hepatitis B x antigen, or HBxAg, contributes importantly to the pathogenesis of hepatocellular carcinoma (HCC). Given that HBxAg constitutively activates beta-catenin and that upregulated ErbB-2 promotes beta-catenin signaling in other tumor types, experiments were designed to ask whether HBxAg was associated with upregulated expression of ErbB-2. When HBxAg positive and negative HepG2 cells were subjected to proteomics analysis, ErbB-2 was shown to be upregulated in HepG2X but not control cells. ErbB-2 was also strongly upregulated in HB infected liver, and weakly in some HCC nodules, where it correlated with HBxAg expression. Among tumor bearing patients, strong ErbB-2 staining in the liver was associated with dysplasia, and a shorter survival after tumor diagnosis. This implies that elevated ErbB-2 is an early marker of HCC. Treatment of HepG2X cells with ErbB-2 specific siRNA not only reduced ErbB-2 expression, but also reduced the expression of beta-catenin, suggesting that ErbB-2 contributed to the stabilization of beta-catenin. ErbB-2 specific siRNA also partially blocked the ability of HBxAg to promote DNA synthesis and growth of HepG2 cells. These results suggest that ErbB-2/beta-catenin up-regulation contributes importantly to the mechanism of HBxAg mediated hepatocellular growth.

Author information

Author/s: Liu, Jie (J); Ahiekpor, Angela (A); Li, Li (L); Li, Xianxing (X); Arbuthnot, Patrick (P); Kew, Michael (M); Feitelson, Mark A (MA);

Affiliation: Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA.

Grants: CA104025 (Agency:NCI NIH HHS) ; CA111427 (Agency:NCI NIH HHS) ; R01 CA104025-04 (Agency:NCI NIH HHS)

Journal and publication information

Publication Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural

Journal: International journal of cancer. Journal international du cancer (Int J Cancer), published in United States. (Language: eng)

Reference: 2009-Oct; vol 125 (issue 8) : pp 1894-901

Dates: Created 2009/08/26; Completed 2009/09/21; Revised 2009/10/16;

PMID: 19610068, status: MEDLINE (last retrieval date: 10/19/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

1-Phosphatidylinositol 3-Kinase - metabolism Adult Blotting, Western Carcinoma, Hepatocellular - metabolism; mortality; secondary Cell Proliferation Female Follow-Up Studies Hepatitis, Chronic - metabolism; pathology Humans Immunoenzyme Techniques Liver - metabolism; pathology Liver Cirrhosis - metabolism; pathology

Liver Neoplasms - metabolism; mortality; pathology Male Middle Aged Neoplasm Staging Prognosis RNA, Messenger - genetics; metabolism RNA, Small Interfering - pharmacology Receptor, erbB-2 - antagonists & inhibitors; genetics; metabolism Retrospective Studies Reverse Transcriptase Polymerase Chain Reaction Trans-Activators - metabolism beta Catenin - metabolism

Associated Chemicals: RNA, Messenger (0) ; RNA, Small Interfering (0) ; Trans-Activators (0) ; beta Catenin (0) ; hepatitis B virus X protein (0) ; Receptor, erbB-2 (EC 2.7.1.112) ; 1-Phosphatidylinositol 3-Kinase (EC 2.7.1.137) ; ERBB2 protein, human (EC 2.7.10.1)

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