These observations suggest a decrease of Igf2 methylation from cirrhosis to HCC in patients with HCV infection, which may be an additional risk factor for HCC.
Abnormal expression of insulin-like growth factor II (IGF-II) is associated with the hepatocyte malignant transformation and hepatocellular carcinoma (HCC) progress.
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 IGF-II abnormality associates with HCC, and circulating IGF-II and IGF-II mRNA are useful molecular markers for HCC differential diagnosis and hematogenous metastasis.
Of the informative HCC samples 47.06% (8 of 17) demonstrated a gain of imprinting of IGF2, and 21.74% (5 of 23) of the informative HCC samples demonstrated a loss of imprinting of H19.
Of the informative HCC samples 47.06% (8 of 17) demonstrated a gain of imprinting of IGF2, and 21.74% (5 of 23) of the informative HCC samples demonstrated a loss of imprinting of H19.
IRS-1, IRS-2, and IRS-4 were each overexpressed in 80% of the HCC samples, and IGF-I and IGF-2 receptors were overexpressed in 40% and 100% of the HCCs, respectively.
The positive frequency of circulating IGF-II mRNA was 34.2% in HCC, no amplified fragment was found in other liver diseases, extrahepatic tumors, and normal controls, respectively.
It may be concluded that IGF II gene expression plays an important role during the development of neoplasia and the gene expresses in the sequence of events leading from glycogen-rich-acidophilic lesions to glycogen poor basophilic lesions to HCC with an expression pattern of "high-low-high" in terms of degree of expression.
Our data suggest that PTEN blocks Sp1 phosphorylation in response to HBx, by inactivating PKC, MAPK and MAPK kinase which eventually downregulate IGF-II expression, during the formation of HCC.