The IGF axis and hepatocarcinogenesis.
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.
Scharf
J G
JG
Department of Medicine, Division of Gastroenterology and Endocrinology, Georg-August-Universität, D-37075 Göttingen, Germany. jscharf@med.uni-goettingen.de
Dombrowski
F
F
Ramadori
G
G
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D002645:Chickens; D010450:Endopeptidases / Q000378:metabolism; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism*; D051379:Mice; D051381:Rats; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D017527:Receptor, IGF Type 2 / Q000378:metabolism; D011972:Receptor, Insulin / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D014407:Tumor Cells, Cultured
D018969:Insulin-Like Growth Factor Binding Proteins; D017527:Receptor, IGF Type 2; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin; D010450:Endopeptidases