Expression and localization of the transforming growth factor-beta type I receptor and Smads in preneoplastic lesions during chemical hepatocarcinogenesis in rats.
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, 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-beta such as TGR1, Smad2, Smad4 and, Smad7 might contribute to the progression of preneoplastic lesions during chemical hepatocarcinogenesis in a rat.
Park
Do Youn
DY
Department of Pathology, College of Medicine Pusan National University, Busan, Korea.
Lee
Chang Hun
CH
Sol
Mee Young
MY
Suh
Kang Suek
KS
Yoon
Sun Young
SY
Kim
Jae Wha
JW
D030201:Activin Receptors, Type I / Q000096:biosynthesis*; D000818:Animals; D017209:Apoptosis; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D018450:Disease Progression; D005982:Glutathione Transferase / Q000378:metabolism; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000139:chemically induced; D008297:Male; D010455:Peptides / Q000737:chemistry; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D051899:Smad2 Protein; D051901:Smad4 Protein; D051906:Smad7 Protein; D013997:Time Factors; D015534:Trans-Activators / Q000096:biosynthesis*
D004268:DNA-Binding Proteins; D010455:Peptides; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D051899:Smad2 Protein; C497784:Smad2 protein, rat; D051901:Smad4 Protein; C490811:Smad4 protein, rat; D051906:Smad7 Protein; C497808:Smad7 protein, rat; D015534:Trans-Activators; D005982:Glutathione Transferase; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625843:Tgfbr1 protein, rat