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Horm Metab Res 2003; 35(11/12): 685-693
DOI: 10.1055/s-2004-814151
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© Georg Thieme Verlag Stuttgart · New York

The Role of the IGF Axis in Hepatocarcinogenesis

J.-G.  Scharf 1 , T.  Braulke 2
  • 1Department of Medicine, Georg-August-Universität, Göttingen, Germany
  • 2Department of Biochemistry, Children’s Hospital, Universitätsklinikum Eppendorf, Hamburg, Germany
Further Information

Publication History

Received 1 September 2003

Accepted after Revision 14 October 2003

Publication Date:
07 January 2004 (online)

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Abstract

Primary hepatocellular carcinoma (HCC) is one of the most common forms of malignant cancer with the fourth highest mortality rate worldwide. Major risk factors for the development of HCC include chronic infections with the hepatitis B or C virus, alcohol consumption, exposure to dietary aflatoxin B1, hereditary liver disease or liver cirrhosis of any etiology. Recent studies have discovered changes in the insulin-like growth factor (IGF) axis that affect the molecular pathogenesis of HCC, including the autocrine production of IGFs, IGF binding proteins (IGFBPs), IGFBP proteases, and IGF receptor expression. Characteristic alterations detected in HCC and hepatoma cell lines comprise the overexpression of IGF-II and the IGF-I receptor emerging as critical events in malignant transformation and growth of tumors. Simultaneous reduction of IGFBP expression and the increase in proteolytic cleavage of IGFBPs result in an excess of bioactive IGFs. Finally, defective functions of the IGF-II/mannose 6-phosphate receptor involved in degradation of IGF II, the activation of the growth inhibitor TGF-β1, and the lysosomal targeting of cathepsin proteases capable to degrade extracellular matrix proteins may contribute to the development of HCC.

Key words

Insulin-like Growth Factors - IGF Binding Proteins - IGF-I Receptor - IGF-II/ Mannose 6-Phosphate Receptor - Hepatocarcinogenesis - Hepatocellular Carcinoma

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PD Dr. med. J.-G. Scharf, M. D.

Zentrum Innere Medizin, Abteilung Gastroenterologie und Endokrinologie

Robert-Koch-Str. 40 · 37075 Göttingen · Germany

Phone: +49(551)398589

Fax: +49(551)392026

Email: jscharf@med.uni-goettingen.de