As the somatostatin analog octreotide suppresses pituitary GH secretion and circulating IGF-1 levels, we examined its effects on human hepatoma (hep G2) cells which selectively express IGFBP-1.
The poorly differentiated hepatoma cell lines PLC/PRF/5 and SK-Hep-1 either did not express or constitutively expressed low basal levels of IGF I, IGF II, and TGF beta, whose mRNA synthesis and abundance showed no response to any heparin-hormone combination.
Radiolabelled IGF-I incubated with serum-free conditioned media from the breast cancer cell line MDA-MB 231 eluted with an apparent M.W. of 35-40 kDa when analyzed by gel filtration chromatography at pH 7.4.The M.W. of this binding activity corresponded to that of BP-25, a binding protein cloned from the hepatocellular carcinoma cell line HepG2.
Only very high concentrations of insulin-like growth factor I and human proinsulin can compete for the insulin receptor binding and suppress HBsAg production, this suggests that insulin may act through its receptor binding to suppress HBsAg expression in human hepatoma Hep3B cells.
We have investigated the expression of insulin-like growth factor I (IGF-I) receptor in human hepatocellular carcinoma cell lines using SNU368 cells containing HBx and SNU387 cells, which lack HBx gene transcript (J-G. Park et al., Int.J.
In the present study, we have investigated the effects of type-I IGF receptor signaling on H4II rat hepatoma cell proliferation, as estimated by 3H-thymidine incorporation into DNA.
As IGF-1R-mediated signaling promotes survival, oncogenic transformation and tumor growth and spread, it represents a potential target for innovative treatment strategies of HCC.
In conclusion, contributions to the malignant phenotype of HCC is due to activation of IGF-I and IGF-II signaling that results in over-expression of both AAH and Notch.
The insulin-like growth factor I (IGF-I)-mediated MAPK cascade is often activated in hepatocellular carcinoma (HCC), but the role of RKIP in the molecular pathogenesis of these tumors is unknown.
Moreover, the inhibition of PI3-kinase completely abolished the nuclear translocation of C/EBPbeta and the up-regulation of GSTalpha protein in IR-HCC treated with IGF-1.
Collectively, these data support the concept for dual IGF-1R/IR targeting in HCC, where EMT status and expressions of IGF-2 and IR may be used to identify those patients who are most likely to benefit from treatment with an IGF-1R/IR dual inhibitor.
Klotho is a tumor suppressor that, through the regulation of IGF-1R phosphorylation and subsequent activation of downstream Akt-p70S6K and ERK signaling, regulates HCC tumor cell proliferation, apoptosis, autophagy and invasion.
The biological consequence of TCF-4J isoform expression was upregulation of genes associated with tripartite Wnt/β-catenin, insulin/IGF-1/IRS1 and Notch signal transduction pathway activation, which contribute to the pathogenesis of HCC.
Low-baseline IGF-I levels independently correlated with shorter TTR and poorer survival in patients with early-stage hepatocellular carcinoma after curative treatment.
Patients with history of HBV infection, who were not treated, and who received multiple palliative treatment for HCC had higher serum IGF-1 mRNA levels (p = 0.03, 0.03, and 0.05, respectively).
In the present study, we report a novel insulin-like growth factor 1 (IGF1) pathway that mediates de novo DNA methylation and TSG (such as DLC1 and CHD5) silencing by upregulation of the DNA methyltransferase 1 (DNMT1) via an AKT/β-transducin repeat-containing protein (βTrCP)-mediated ubiquitin-proteasome pathway in HCC.
The effects of IL6/IGFI on stemness expression in HCC were examined using OCT4/NANOG promoter luciferase reporter, RNA interference, secondary sphere formation, side population, and xenograft animal models.