The insulin-like growth factor (IGF) signaling axis and hepatitis C virus-associated carcinogenesis (Review)

Kasprzak,Aldona; Adamek,Agnieszka

doi:10.3892/ijo.2012.1666

The insulin-like growth factor (IGF) signaling axis and hepatitis C virus-associated carcinogenesis (Review)

Authors:
- Aldona Kasprzak
- Agnieszka Adamek
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Affiliations: Department of Histology and Embryology, University of Medical Sciences, 60-781 Poznań, Poland , Department of Infectious Diseases, University of Medical Sciences, 61-285 Poznań, Poland
Published online on: October 16, 2012 https://doi.org/10.3892/ijo.2012.1666
Pages: 1919-1931

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Abstract

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.

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