Induction of p53 and Bax during TGF-beta 1 initiated apoptosis in rat liver epithelial cells

Biochem Biophys Res Commun. 1998 Oct 9;251(1):56-60. doi: 10.1006/bbrc.1998.9411.

Abstract

The relationship between transforming growth factor-beta1 (TGF-beta1) induced growth arrest and apoptosis in rat liver derived epithelial (RLE) cells was analyzed. TGF-beta1 treatment of RLE cells induced both cell cycle arrest and apoptosis. However, pretreatment of the cells with either dexamethasone or cyclohexamide suppressed TGF-beta1 induced apoptosis, without preventing the cell cycle arrest. Both p53 and Bax were subsequently shown to be overexpressed during the TGF-beta1 induced apoptosis. Furthermore, it was revealed that cycloheximide suppressed expression of both p53 and Bax. In contrast, dexamethasone treatment prevented Bax expression alone. Treatment of RLE cells with several growth factors either alone or in combination was ineffective in counteracting TGF-beta1 induced apoptosis. In additon, we show that TGF-alpha also induced both p53 and Bax expressions and augmented TGF-beta-induced apoptosis. Thus, p53 and Bax are likely to be key factors in TGF-beta1 induced apoptosis in RLE cells.

MeSH terms

  • Animals
  • Apoptosis*
  • Cell Cycle / drug effects
  • Cell Line, Transformed
  • Cells, Cultured
  • Down-Regulation / drug effects
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism*
  • NF-kappa B / metabolism
  • Proto-Oncogene Proteins / biosynthesis*
  • Proto-Oncogene Proteins c-bcl-2*
  • Rats
  • Transforming Growth Factor beta / physiology*
  • Tumor Suppressor Protein p53 / biosynthesis*
  • bcl-2-Associated X Protein

Substances

  • Bax protein, rat
  • NF-kappa B
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Transforming Growth Factor beta
  • Tumor Suppressor Protein p53
  • bcl-2-Associated X Protein