Display Settings:

Format

Send to:

Choose Destination
We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Dig Dis. 2009;27(2):93-101. doi: 10.1159/000218340. Epub 2009 Jun 22.

Hypotheses on the role of transforming growth factor-beta in the onset and progression of hepatocellular carcinoma.

Author information

  • 1Department of Medicine II, Faculty of Medicine at Mannheim, University of Heidelberg, Mannheim, Germany. steven.dooley@medma.uni-heidelberg.de

Abstract

Hepatocellular carcinomas (HCCs) constitute a therapeutic challenge with mostly unfavorable outcome. This may reflect our incomplete understanding of disease pathogenesis, e.g. the elucidation of tumorigenic signaling pathways. Knowledge gathered hitherto focuses on genetic alterations that result in the loss of tumor suppressor functions as well as amplification and mutation of cancer genes. Further evidence points to a decisive role of cytostatic and apoptotic functions mediated on hepatocytes by transforming growth factor (TGF)-beta. These effects are critical for the control of liver mass with loss of TGF-beta activities resulting in hyperproliferative disorders and cancer. This concept is based on studies that describe a bipartite role of TGF-beta with tumor suppressor functions at early stages of liver damage and regeneration, whereas during cancer progression TGF-beta may turn from a tumor suppressor to a tumor promoter that exacerbates invasive and metastatic behavior. Consequently and most importantly, the oncogenic potential of recent therapeutic approaches against profibrogenic TGF-beta effects needs to be carefully delineated and a cancer therapy with specific targets disrupting the TGF-beta signaling cascade may be envisioned. In line with this concept, we and others found overexpression of TGF-beta antagonist Smad7 in the majority of HCC samples, providing a mechanism for hepatocytes to escape TGF-beta-dependent growth control in the process of cancerogenesis.

Copyright 2009 S. Karger AG, Basel.

PMID:
19546546
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for S. Karger AG, Basel, Switzerland
    Loading ...
    Write to the Help Desk