화학적으로 유도한 백서 간암에서 TGF-β1 및 TGF-β type II receptor의 발현

Abstract

Background : Transforming growth factor (TGF)-β1 inhibits hepatocyte proliferation by inducing apoptosis. Expression of TGF-β1 is tightly associated with the TGF-β type II receptor (TGR2) expression level, and has been regarded as an important change of TGF-β1 and TGR2 during hepatocarcinogenesis. We investigated the gene expressions and protein localizations of TGF-β1 and TGR2 in chemical hepatocarcinogenesis. Methods : Solt and Farber’s method was used as the chemical hepatocarcinogenesis model of the rat. Northern blot analyses and immunohistochemistry for TGF-β1 and TGR2 were performed to investigate the gene expressions and protein localizations, respectively. Results : The Northern blot analyses showed a slight increase of TGF-β1 transcripts one month after partial hepatectomy, which is more than in sham operated control liver, and a decrease of transcripts for TGR2 two months after partial hepatectomy. The number of TGF-β1-positive preneoplastic hepatocytes was increased and correlated with the increase of the number of TGR2 negative hepatocytes or reduction of expressions of TGR2 in preneoplastic lesions. HCC tissues showed an increase of TGF-β1 protein expressions and a decrease of TGR2 compared to the adjacent liver parenchyme. Conclusion : Our data suggest that down regulation of TGR2 in preneoplastic lesions and HCC might contribute to the resistance to the growth inhibitory effects of TGF-β1.