Role of c-kit receptor tyrosine kinase in development of oval cells in the rat 2-acetylaminofluorene/partial hepatectomy model.
Oval cells that develop in the rat 2-acetylaminofluorene/partial hepatectomy (AAF/PH) model express the c-kit receptor tyrosine kinase (KIT) and its ligand, stem cell factor (SCF). We investigated the role of the SCF/KIT system in the development of oval cells using Ws/Ws rats, whose c-kit kinase activity was severely impaired owing to a small deletion in the kinase domain. On days 7, 9, and 13 after PH in the AAF/PH model, the development of oval cells was remarkably suppressed in Ws/Ws rats when compared with that of the control normal (+/+) rats. However, oval cells that developed in Ws/Ws rats expressed marker proteins of oval cells, such as alpha-fetoprotein (AFP), cytokeratin-19 (CK-19), and flt-3 receptor tyrosine kinase, similar to those of +/+ rats. Furthermore, labeling with [3H]-thymidine and immunostaining of Ki-67 showed that the proliferative activity of oval cells that developed in Ws/Ws rats was comparable with that of +/+ rats. The present results indicate that the signal transduction of the SCF/KIT system plays a crucial role in the development of oval cells, at least, in the rat AAF/PH model, and suggest that KIT-mediated signal transduction plays only a small role in determining the phenotype and in the proliferative activity of oval cells.
First Department of Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
S
S
Matsusaka
T
T
Tsujimura
A
A
Toyosaka
K
K
Nakasho
A
A
Sugihara
E
E
Okamoto
K
K
Uematsu
N
N
Terada
D015073:2-Acetylaminofluorene / Q000494:pharmacology*; D000818:Animals; D006498:Hepatectomy / Q000379:methods*; D008099:Liver / Q000187:drug effects* / Q000473:pathology*; D008297:Male; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000502:physiology*; D051381:Rats / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000502:physiology*; D012016:Reference Values
D015073:2-Acetylaminofluorene; D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases