pRb2/p130 promotes radiation-induced cell death in the glioblastoma cell line HJC12 by p73 upregulation and Bcl-2 downregulation

Oncogene. 2002 Aug 29;21(38):5897-905. doi: 10.1038/sj.onc.1205750.

Abstract

This study shows that in the glioblastoma hamster cell line HJC12 the retinoblastoma family member pRb2/p130 enhances gamma-radiation-induced cell death. In HJC12 cells the tetracycline-regulated expression of pRb2/p130 increased the percentage of gamma-radiation-induced apoptotic cells from 27 to 47%. pRb2/p130 overexpression was associated with the downregulation of the anti-apoptotic factor Bcl-2 and the upregulation of the steady-state protein levels of the pro-apoptotic transcription factor p73. In particular, RT-PCR showed a significant increase in the expression of the p73delta isoform when pRb2/p130 was overexpressed. The ability of pRb2/p130 to modulate apoptosis was not associated with its role in mediating G0/G1 arrest during cell cycle progression. Our data suggest a role for pRb2/p130 in glioblastoma gamma-radiation-induced cell death, indicating that the antitumoral action of pRb2/p130 can regulate both inhibition of cell cycle progression and induction of cell death.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis / radiation effects
  • Cell Death / radiation effects
  • Central Nervous System Neoplasms / metabolism*
  • Central Nervous System Neoplasms / pathology
  • Central Nervous System Neoplasms / radiotherapy
  • Cricetinae
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • DNA-Binding Proteins / radiation effects
  • Down-Regulation
  • G1 Phase / radiation effects
  • Gamma Rays
  • Gene Expression Regulation, Neoplastic
  • Genes, Tumor Suppressor
  • Glioblastoma / metabolism*
  • Glioblastoma / pathology
  • Glioblastoma / radiotherapy
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Nuclear Proteins / radiation effects
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • Phosphoproteins / radiation effects
  • Proteins*
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / radiation effects
  • Retinoblastoma-Like Protein p130
  • Tumor Cells, Cultured
  • Tumor Protein p73
  • Tumor Suppressor Proteins

Substances

  • DNA-Binding Proteins
  • Nuclear Proteins
  • Phosphoproteins
  • Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Retinoblastoma-Like Protein p130
  • Tumor Protein p73
  • Tumor Suppressor Proteins