Review

The IGF axis and hepatocarcinogenesis

J-G Scharf¹, F Dombrowski² and G Ramadori¹

¹ Department of Medicine, Division of Gastroenterology and Endocrinology, Georg- August-Universität, D-37075 Göttingen, Germany
² Institute of Pathology, Rheinische Friedrich- Wilhelms-Universität, D-53127 Bonn, Germany

Correspondence to:
Dr Scharf, Department of Medicine, Division of Gastroenterology and Endocrinology, Robert-Koch-Str. 40, D-37075 Göttingen, Germany jscharf{at}med.uni-goettingen.de

Deregulation of the insulin-like growth factor (IGF) axis, including the autocrine production of IGFs, IGF binding proteins (IGFBPs), IGFBP proteases, and the expression of the IGF receptors, has been identified in the development of hepatocellular carcinoma (HCC). Characteristic alterations detected in HCC and hepatoma cell lines comprise the increased expression of IGF-II and the IGF-I receptor (IGF-IR), which have emerged as crucial events in malignant transformation and the growth of tumours. Alterations of IGFBP production and the proteolytic degradation of IGFBPs resulting in an excess of bioactive IGFs, as well as the defective function of the IGF degrading IGF-II/mannose 6-phosphate receptor (IGF-II/M6PR), may further potentiate the mitogenic effects of IGFs in the development of HCC.

Key Words: insulin-like growth factors • insulin-like growth factor binding proteins • insulin-like growth factor I receptor • insulin-like growth factor II/mannose 6-phosphate receptor • hepatocarcinogenesis • hepatocellular carcinoma

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Cheng, W., Tseng, C.-J., Lin, T. T.C., Cheng, I., Pan, H.-W., Hsu, H.-C., Lee, Y.-M. (2008). Glypican-3-mediated oncogenesis involves the Insulin-like growth factor-signaling pathway. Carcinogenesis 29: 1319-1326 [Abstract] [Full Text]  
• Lee, J. Y., Han, C. Y., Yang, J. W., Smith, C., Kim, S. K., Lee, E. Y.-H. P., Kim, S. G., Kang, K. W. (2007). Induction of Glutathione Transferase in Insulin-Like Growth Factor Type I Receptor-Overexpressed Hepatoma Cells. Mol. Pharmacol. 72: 1082-1093 [Abstract] [Full Text]  
• Nishikawa-Ogawa, M., Wanibuchi, H., Morimura, K., Kinoshita, A., Nishikawa, T., Hayashi, S., Yano, Y., Fukushima, S. (2006). N-acetylcysteine and S-methylcysteine inhibit MeIQx rat hepatocarcinogenesis in the post-initiation stage. Carcinogenesis 27: 982-988 [Abstract] [Full Text]  
• Sangwan, V., Paliouras, G. N., Cheng, A., Dube, N., Tremblay, M. L., Park, M. (2006). Protein-tyrosine Phosphatase 1B Deficiency Protects against Fas-induced Hepatic Failure. J. Biol. Chem. 281: 221-228 [Abstract] [Full Text]  
• Fischer, A. N.M., Herrera, B., Mikula, M., Proell, V., Fuchs, E., Gotzmann, J., Schulte-Hermann, R., Beug, H., Mikulits, W. (2005). Integration of Ras subeffector signaling in TGF-{beta} mediated late stage hepatocarcinogenesis. Carcinogenesis 26: 931-942 [Abstract] [Full Text]  
• Wu, J. D., Odman, A., Higgins, L. M., Haugk, K., Vessella, R., Ludwig, D. L., Plymate, S. R. (2005). In vivo Effects of the Human Type I Insulin-Like Growth Factor Receptor Antibody A12 on Androgen-Dependent and Androgen-Independent Xenograft Human Prostate Tumors. Clin. Cancer Res. 11: 3065-3074 [Abstract] [Full Text]  
• Malarkey, D. E., Parker, J. S., Turman, C. A., Scott, A. M., Paules, R. S., Collins, J., Maronpot, R. R. (2005). Microarray Data Analysis of Mouse Neoplasia. Toxicol Pathol 33: 127-135 [Abstract] [Full Text]  
• Evert, M., Sun, J., Pichler, S., Slavova, N., Schneider-Stock, R., Dombrowski, F. (2004). Insulin Receptor, Insulin Receptor Substrate-1, Raf-1, and Mek-1 during Hormonal Hepatocarcinogenesis by Intrahepatic Pancreatic Islet Transplantation in Diabetic Rats. Cancer Res. 64: 8093-8100 [Abstract] [Full Text]  
• Boutin, S. R., Rogers, A. B., Zeli Shen, , Fry, R. C., Love, J. A., Nambiar, P. R., Suerbaum, S., Fox, J. G. (2004). Hepatic Temporal Gene Expression Profiling in Helicobacter hepaticus-Infected A/JCr Mice. Toxicol Pathol 32: 678-693 [Abstract]  
• Wu, X., Zhao, H., Do, K.-A., Johnson, M. M., Dong, Q., Hong, W. K., Spitz, M. R. (2004). Serum Levels of Insulin Growth Factor (IGF-I) and IGF-Binding Protein Predict Risk of Second Primary Tumors in Patients with Head and Neck Cancer. Clin. Cancer Res. 10: 3988-3995 [Abstract] [Full Text]  
• Liu, J., Xie, Y., Ward, J. M., Diwan, B. A., Waalkes, M. P. (2004). Toxicogenomic Analysis of Aberrant Gene Expression in Liver Tumors and Nontumorous Livers of Adult Mice Exposed in utero to Inorganic Arsenic. Toxicol Sci 77: 249-257 [Abstract] [Full Text]  
• Yadetie, F., Laegreid, A., Bakke, I., Kusnierczyk, W., Komorowski, J., Waldum, H. L., Sandvik, A. K. (2003). Liver gene expression in rats in response to the peroxisome proliferator-activated receptor-{alpha} agonist ciprofibrate. Physiol. Genomics 15: 9-19 [Abstract] [Full Text]  
• Anders, R. A., Yerian, L. M., Tretiakova, M., Davison, J. M., Quigg, R. J., Domer, P. H., Hoberg, J., Hart, J. (2003). cDNA Microarray Analysis of Macroregenerative and Dysplastic Nodules in End-Stage Hepatitis C Virus-Induced Cirrhosis. Am. J. Pathol. 162: 991-1000 [Abstract] [Full Text]  
• Choi, Y., Kawazoe, Y., Murakami, K., Misawa, H., Uesugi, M. (2003). Identification of Bioactive Molecules by Adipogenesis Profiling of Organic Compounds. J. Biol. Chem. 278: 7320-7324 [Abstract] [Full Text]  
• Araki, Y., Okamura, S., Hussain, S. P., Nagashima, M., He, P., Shiseki, M., Miura, K., Harris, C. C. (2003). Regulation of Cyclooxygenase-2 Expression by the Wnt and Ras Pathways. Cancer Res. 63: 728-734 [Abstract] [Full Text]  
• Bode, B. P., Fuchs, B. C., Hurley, B. P., Conroy, J. L., Suetterlin, J. E., Tanabe, K. K., Rhoads, D. B., Abcouwer, S. F., Souba, W. W. (2002). Molecular and functional analysis of glutamine uptake in human hepatoma and liver-derived cells. Am. J. Physiol. Gastrointest. Liver Physiol. 283: G1062-G1073 [Abstract] [Full Text]