Expression and Localization of the Transforming Growth Factor-beta Type I receptor and Smads in Preneoplastic Lesions during Chemical Hepatocarcinogenesis in Rats

Abstract

Little is known about the involvement of Smad-related molecules in the regulation of the Transforming Growth Factor (TGF)-signaling pathway during hepatocarcinogenesis, particularly with respect to preneoplastic lesions of a rat liver. The aims of this study were to investigate the localizations and temporal expressions of TGF-Receptor Type 1 (TGR1) and Smads during the promotion stage of chemical hepatocarcinogenesis in rats. We investigated expressions and localizations of TGR1, Smad2, Smad4, and Smad7 by using semi-quantitative RT-PCR and immunohistochemistry in preneoplastic lesions during rat chemical hepatocarcinogenesis induced by Solt and Farber's method. The down-regulation of TGR1, Smad2, and Smad4 was evident during the later steps of the promotion stage of chemical hepatocarcinogenesis. In contrast with other Smads, increased Smad7 expression was evident during the later steps of the promotion stage. Also immunohistochemistry revealed that the main site of TGR1, Smad2, Smad4, and Smad7 expression was mainly in hepatocytes of the preneoplastic lesions of a rat liver. Dysregulation of the downstream effectors of TGF-such as TGR1, Smad2, Smad4 and, Smad7 might contribute to the progression of preneoplastic lesions during chemical hepatocarcinogenesis in a rat.

Cross-talk between IFN-α and TGF-β1signaling pathways in preneoplastic rat liver

“…Autocrine TGF-b 1 is known to suppress tumorigenesis and tumor progression in normal and early transformed cells, but it can also promote the survival of various cancer cells (Lei et al 2007). Besides, dysregulation of the downstream effectors of TGF-b has been described in late steps of promotion stage, that may contribute to the progression of preneoplastic lesions (Park et al 2003).…”

Dissection of Signal Transduction Pathways as a Tool for the Development of Targeted Therapies of Hepatocellular Carcinoma

“…2). Up-regulation of Tgf-receptor type 1 (Tfg -R1), Smad 2, Smad4, and Smad7, in FAH, during and after 2-acetylaminofluorene feeding in rats treated according to the RH model, is followed by a decrease in expression of Tgf -R1 and its effector proteins Smad2 and Smad4, whereas Smad7, which inhibits Tfg-R1 activity, progressively increases [63].…”

Smad7 attenuates TGF-β-mediated aging-related hypofunction of submandibular glands

“…13 Smad7 has an inhibitory effect on TGFb-induced fibrosis in other organs. 14,15 However, the role of the TGF-b/Smad pathway and Smad7 in the agingrelated SMG hypofunction remains unclear. Therefore, this study aims to reveal the position of TGF-b/Smad in the aging-related SMG hypofunction.…”