Expression of transforming growth factor (TGF)-beta1 and TGF-beta type II receptor in preneoplastic lesions during chemical hepatocarcinogenesis of rats.

摘要

Transforming growth factor (TGF)-beta1 is an important apoptotic growth inhibitor of hepatocyte proliferation, and the expression of TGF-beta1, which regulates cell proliferation, is closely associated with the expression level of TGF-beta type II receptor (TGR2). Moreover, TGF-beta1 expression has been regarded to be an important change in hepatocarcinogenesis, We undertook this study to investigate the gene expression and protein localization of TGF-beta1 and TGR2 and their relationship with apoptosis in the chemically induced hepatocarcinogenesis of the rat, as produced using Solt and Farber's method, during the promotion stage (up to 56 days after partial hepatectomy). Northern blot analysis showed a slight, but not a significant, increase in TGF-beta1 transcripts, and a significant decrease in the TGR2 transcripts during the later stage of our experiments (42 days after partial hepatectomy). Immunohistochemical study showed that TGF-beta1-positive preneoplastic hepatocytes increased with time, and this correlated with an increase of TGR2 negative or reduced TGR2 expressed preneoplastic lesions. The TUNEL method revealed that apoptotic cells increased with time and were more numerous in the adjacent liver parenchyme than preneoplastic lesions. Our data suggest that the expressions of TGF-beta1 and TGR2 are significantly altered during the promotion stage of hepatocarcinogenesis of rat and that these changes might contribute to the development and progression of preneoplastic lesions.