J Korean Med Sci.  2003 Aug;18(4):510-519. 10.3346/jkms.2003.18.4.510.

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

• Park DY
• Lee CH
• Sol MY
• Suh KS
• Yoon SY
• Kim JW

• KMID: 648902
• DOI: http://doi.org/10.3346/jkms.2003.18.4.510

Abstract

Little is known about the involvement of Smad-related molecules in the regulation of the Transforming Growth Factor (TGF)-beta 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-beta 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, Sma-d2, 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-beta such as TGR1, Smad2, Smad4 and, Smad7 might contribute to the progression of preneoplastic lesions during chemical hepatocarcinogenesis in a rat.

Keyword

Receptors; Transforming Growth Factor Beta; Signal Transduction; Precancerous Condi-tions; Carcinogens; Liver; Rats

MeSH Terms

Activin Receptors, Type I/*biosynthesis
Animals
Apoptosis
DNA-Binding Proteins/*biosynthesis
Disease Progression
Glutathione Transferase/metabolism
Immunohistochemistry
In Situ Nick-End Labeling
Liver/metabolism
Liver Neoplasms/chemically induced
Male
Peptides/chemistry
RNA, Messenger/metabolism
Rats
Rats, Sprague-Dawley
Receptors, Transforming Growth Factor beta/*biosynthesis
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction
Time Factors
Trans-Activators/*biosynthesis