The insulin-like growth factor (IGF) signaling axis and hepatitis C virus-associated carcinogenesis (review).
Insulin-like growth factor (IGF) signaling plays an important autocrine,             paracrine and endocrine role in growth promotion involving various tissues and             organs. Synthesis of both IGFs (IGF-1 and IGF-2) in normal conditions takes place             mainly in the liver even if the proteins can be produced in every cell of the             human body. The alterations in the IGF signaling axis in human hepatocarcinogenesis             are described, but mechanisms of the interactions between expression of oncogenic             hepatitis C virus (HCV) proteins and components of the IGF system in progression             of chronic hepatitis C to primary hepatocellular carcinoma (HCC) have been poorly             recognised. In advanced stages of liver diseases, lowered serum levels of IGF-1             and IGF-2 have been documented. This was supposed to reflect significant damage             to liver parenchyma, a decreased number of growth hormone receptors and a decreased             genomic expression of IGF binding proteins (IGF BPs). In HCC, a decreased tissue             expression of IGF-1, and an increased expression of IGF-1 receptor (IGF-1R) were             noted, compared to the control. Potential mechanisms of augmented IGF-2 expression             in HCC were also described and dysregulation of IGF signaling in HCC was concluded             to occur predominantly at the level of IGF-2 bioavailability. The review aimed             at presentation of involvement of IGF-1, IGF-1R and IGF BPs (mostly IGF BP-3 and             IGF BP-6) in HCV-related hepatocarcinogenesis. Manifestation of various mRNA transcripts             and IGF-1 proteins and their potential involvement in carcinogenesis are also             discussed.
Department of Histology and Embryology, University of Medical Sciences, 60-781 Poznań, Poland. akasprza@ump.edu.pl
Aldona
A
Kasprzak
Agnieszka
A
Adamek
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002472:Cell Transformation, Viral; D016679:Genome, Viral; D016174:Hepacivirus / Q000235:genetics / Q000472:pathogenicity*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D015398:Signal Transduction; D013002:Somatomedins / Q000235:genetics / Q000378:metabolism*
D013002:Somatomedins