Cellular commitment to oncogene-induced transformation or apoptosis is dependent on the transcription factor IRF-1

Cell. 1994 Jun 17;77(6):829-39. doi: 10.1016/0092-8674(94)90132-5.


The transcriptional activator interferon regulatory factor 1 (IRF-1) and its antagonistic repressor IRF-2 are regulators of the interferon (IFN) system and of cell growth. Here we report that embryonic fibroblasts (EFs) from mice with a null mutation in the IRF-1 gene (IRF-1-/- mice) can be transformed by expression of an activated c-Ha-ras oncogene. This property is not observed in EFs from wild-type or IRF-2-/- mice but is still observed in EFs from mice deficient in both genes. The transformed phenotype of ras-expressing IRF-1-/- EFs could be suppressed by the expression of the IRF-1 cDNA. Thus, IRF-1 functions as a tumor suppressor. Furthermore, expression of the c-Ha-ras oncogene causes wild-type but not IRF-1-/- EFs to undergo apoptosis when combined with a block to cell proliferation or treated by anticancer drugs or ionizing radiation. Hence, IRF-1 may be a critical determinant of oncogene-induced cell transformation or apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Apoptosis / genetics
  • Apoptosis / physiology*
  • Base Sequence
  • Cell Line
  • Cell Survival / drug effects
  • Cell Survival / radiation effects
  • Cell Transformation, Neoplastic / genetics*
  • DNA
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Genes, ras*
  • Interferon Regulatory Factor-1
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Molecular Sequence Data
  • Mutation
  • Neoplasms, Experimental / etiology
  • Phosphoproteins / metabolism*
  • Transcription Factors / metabolism*


  • Antineoplastic Agents
  • DNA-Binding Proteins
  • Interferon Regulatory Factor-1
  • Irf1 protein, mouse
  • Phosphoproteins
  • Transcription Factors
  • DNA