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Semin Liver Dis 1998; 18(2): 115-122
DOI: 10.1055/s-2007-1007148
ORIGINAL ARTICLE

© 1998 by Thieme Medical Publishers, Inc.

Dysregulation of Apoptosis in Hepatocellular Carcinoma

Snorri S. Thorgeirsson, Tadahisa Teramoto, Valentina M. Factor
  • Laboratory of Experimental Carcinogenesis, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
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Publication History

Publication Date:
17 March 2008 (online)

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ABSTRACT

The tightly controlled homeostatic mechanisms between cell growth and apoptosis that exist in normal liver tissue are disrupted during hepatocarcinogenesis. The TGF (transforming growth factor)-β signaling system is a central component of the mechanisms by which cell growth and apoptosis are controlled in the liver. The recent delineation of the TGF-β signaling pathway has provided a unique framework for analysis of the impact that disruption of individual components of this signaling pathway can have on apoptosis during hepatocarcinogenesis. Here we review recent data on involvement of the TGF-β signaling pathway in the dysregulation of apoptosis frequently observed in hepatocellular carcinomas. The data indicate that disruption of the TGF-β pathway at the pre-receptor, receptor, and post-receptor levels occurs in hepatocellular carcinomas and can cause dysregulation of apoptosis. Also, substantial evidence now exists that phosphatidylinositol-3-kinase (PI3K) may function as an important negative regulator of the TGF-β1-induced apoptosis in hepatocellular carcinomas. Taken together, the available evidence indicates that disruption of the TGF-β1-induced apoptosis as well as growth inhibition is an important and integral part of the multistage process of liver carcino gene sis.

KEY WORDS

apoptosis - TGF-β - liver - carcinoma - proliferation

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