Ionizing radiation activates expression of FOXO3a, Fas ligand, and Bim, and induces cell apoptosis

Int J Oncol. 2006 Sep;29(3):643-8.

Abstract

Genotoxic stress such as ionizing radiation can induce DNA damage and promote cell-cycle arrest or apoptosis through either a p53-dependent or -independent pathway. Recently, members of the FOXO Forkhead transcription factor family have been implicated in playing a role in both DNA repair and apoptosis in mammalian cells that promoted us to examine the role of FOXO transcription factors in ionizing radiation-induced apoptosis. Here, we show that ionizing radiation can promote FOXO3a (FKHRL1) transcriptional activity and protein expression level, and induce nuclear translocation of FOXO3a in Saos2, a p53-null osteosarcoma cell line. Ionizing radiation stimulates expression of apoptosis-inducing proteins such as Fas ligand and the Bcl-2 interacting mediator of cell death (Bim) leading to cellular apoptosis. The observed upregulation of proapoptotic genes and apoptosis in cells without p53 in response to ionizing radiation suggests a novel p53-independent mechanism underlying ionizing radiation-induced apoptosis in cancer cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / radiation effects*
  • Apoptosis Regulatory Proteins / metabolism*
  • Bcl-2-Like Protein 11
  • Bone Neoplasms / metabolism
  • Bone Neoplasms / radiotherapy
  • Cell Nucleus / metabolism
  • Cell Nucleus / radiation effects
  • Cells, Cultured
  • Fas Ligand Protein
  • Forkhead Box Protein O3
  • Forkhead Transcription Factors / metabolism*
  • Gene Expression Regulation / radiation effects*
  • Humans
  • Kidney / metabolism
  • Kidney / radiation effects
  • Membrane Glycoproteins / metabolism*
  • Membrane Proteins / metabolism*
  • Osteosarcoma / metabolism*
  • Osteosarcoma / radiotherapy
  • Promoter Regions, Genetic
  • Protein Transport / radiation effects
  • Proto-Oncogene Proteins / metabolism*
  • Radiation, Ionizing
  • Transcription, Genetic / radiation effects
  • Tumor Necrosis Factors / metabolism*
  • Tumor Suppressor Protein p53 / metabolism
  • Up-Regulation

Substances

  • Apoptosis Regulatory Proteins
  • BCL2L11 protein, human
  • Bcl-2-Like Protein 11
  • FASLG protein, human
  • FOXO3 protein, human
  • Fas Ligand Protein
  • Forkhead Box Protein O3
  • Forkhead Transcription Factors
  • Membrane Glycoproteins
  • Membrane Proteins
  • Proto-Oncogene Proteins
  • Tumor Necrosis Factors
  • Tumor Suppressor Protein p53