Role of c-kit receptor tyrosine kinase in development of oval cells in the rat 2-acetylaminofluorene/partial hepatectomy model

Hepatology. 1999 Mar;29(3):670-6. doi: 10.1002/hep.510290304.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Acetylaminofluorene / pharmacology*
  • Animals
  • Hepatectomy / methods*
  • Liver / drug effects*
  • Liver / pathology*
  • Male
  • Proto-Oncogene Proteins c-kit / genetics
  • Proto-Oncogene Proteins c-kit / physiology*
  • Rats / genetics
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / physiology*
  • Reference Values

Substances

  • 2-Acetylaminofluorene
  • Proto-Oncogene Proteins c-kit
  • Receptor Protein-Tyrosine Kinases