Interferon regulatory factor 4 binding protein is a novel p53 target gene and suppresses cisplatin-induced apoptosis of breast cancer cells

Mol Cancer. 2012 Aug 13:11:54. doi: 10.1186/1476-4598-11-54.

Abstract

Background: Our previous work demonstrated that ectopic expression of interferon regulatory factor 4 binding protein (IBP) was correlated with the malignant behaviour of human breast cancer cells. The mechanisms controlling differential expression of IBP in breast cancer still remain unknown.

Results: To investigate the mechanism of IBP dysregulation in breast cancer, we identified IBP was a novel p53 target gene. IBP expression was negatively regulated by wild-type p53 and was p53 dependently suppressed by DNA damage agent cisplatin. Furthermore, high levels of IBP were found to decrease cisplatin-induced growth suppression and apoptotic cell death, which was associated with decreased p53 activity and imbalanced Bcl-2 family member expression.

Conclusions: IBP is a novel p53 target gene which suppresses cisplatin-mediated apoptosis of breast cancer cells via negative feedback regulation of the p53 signalling pathway, suggesting IBP may serve as a target for pharmacologic intervention of breast cancer resistant to cisplatin therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects*
  • Apoptosis / genetics*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism*
  • Cell Line, Tumor
  • Cisplatin / pharmacology*
  • DNA Damage / drug effects
  • DNA-Binding Proteins / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Guanine Nucleotide Exchange Factors / genetics*
  • Humans
  • Nuclear Proteins / genetics*
  • Promoter Regions, Genetic
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA Interference
  • Signal Transduction
  • Transcriptional Activation
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • Antineoplastic Agents
  • DEF6 protein, human
  • DNA-Binding Proteins
  • Guanine Nucleotide Exchange Factors
  • Nuclear Proteins
  • Tumor Suppressor Protein p53
  • Proto-Oncogene Proteins c-akt
  • Cisplatin