Expressions of transforming growth factor (TGF)-β1 and TGF-β type II receptor and their relationship with apoptosis during chemical hepatocarcinogenesis

The expression of transforming growth factor (TGF)-beta1, which regulates cell proliferation, is tightly associated with that of TGF-beta type 11 receptor (TGR2), and has been regarded as an important change during hepatocarcinogenesis. Our aim in this study was to investigate the expression and localization of TGF-beta1 and TGR2 and to determine their relationships with apoptosis in chemical hepatocarcinogenesis of the rat produced by Solt and Farber's method. Northern blot analysis showed that a slight increase of TGF-beta1 transcripts and a decrease of TGR2 transcripts during hepatocarcinogenesis. Immunohistochemistry revealed that TGF-beta1-positive preneoplastic hepatocytes increased with time, and that this correlated with a reduction TGR2 expressing preneoplastic lesions. Hepatocellular carcinoma (HCC) tissues showed higher levels of TGF-beta1 transcripts and protein and lower levels of TGR2 transcripts and protein compared to the paired adjacent liver parenchyme. TUNEL revealed that apoptotic cells increased with time and were more numerous in the adjacent liver parenchyme than in preneoplastic lesions and HCC tissues. Our data suggest that the down regulation of TGR2 in preneoplastic lesions and HCC tissues might contribute to resistance to the growth inhibitory effects of TGF-beta1, and to the roles of TGF-beta1 in the development and progression of preneoplastic lesions and HCC in a chemically induced rat hepatocarcinogensis model. (C) 2003 Elsevier B.V. All rights reserved.