Expression and Localization of the Transforming Growth Factor-beta Type I receptor and Smads in Preneoplastic Lesions during Chemical Hepatocarcinogenesis in Rats.
10.3346/jkms.2003.18.4.510
- Author:
Do Youn PARK
1
;
Chang Hun LEE
;
Mee Young SOL
;
Kang Suek SUH
;
Sun Young YOON
;
Jae Wha KIM
Author Information
1. Department of Pathology, College of Medicine Pusan National University, Busan, Korea. pdy220@pusan.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
Receptors;
Transforming Growth Factor Beta;
Signal Transduction;
Precancerous Condi-tions;
Carcinogens;
Liver;
Rats
- MeSH:
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
- From:Journal of Korean Medical Science
2003;18(4):510-519
- CountryRepublic of Korea
- Language:English
-
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.
