Butyrate response factor 1 enhances cisplatin sensitivity in human head and neck squamous cell carcinoma cell lines

Int J Cancer. 2005 Oct 20;117(1):32-40. doi: 10.1002/ijc.21133.


Cisplatin is a widely used chemotherapeutic agent in head and neck squamous cell carcinoma (HNSCC). Resistance to cisplatin is a common feature of HNSCC. To identify genes that may regulate cisplatin sensitivity, we carried out a cDNA microarray analysis of gene expression in cisplatin-sensitive and cisplatin-resistant HNSCC-derived cell lines. Among genes differentially expressed by cisplatin treatment, we have confirmed the elevated expression of butyrate responsive factor 1 (BRF1) in cisplatin-sensitive HNSCC cells and have demonstrated that the expression level of BRF1 is associated with cisplatin-sensitivity. Specific inhibition of BRF1 expression using an antisense oligodeoxynucleotide (ODN) decreased the cisplatin-sensitivity and, on the contrary, overexpression of BRF1 increased cisplatin-sensitivity in HNSCC cells. Elevated expression of BRF1 decreased the level of the human inhibitor of apoptosis protein-2 (cIAP2) and increased the caspase-3 activity in HNSCC cells. In addition, elevated expression of BRF1 decreased the expression level of enhanced green fluorescent protein (EGFP) linked to a 3' terminal AU-rich element (ARE) of cIAP2 mRNA. These findings demonstrate that BRF1 expression enhanced cisplatin sensitivity in HNSCC cells by reducing the levels of cIAP2 mRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Apoptosis
  • Base Sequence
  • Biomarkers, Tumor / metabolism
  • Butyrate Response Factor 1
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • Caspase 3
  • Caspases / metabolism
  • Cisplatin / therapeutic use*
  • DNA-Binding Proteins / antagonists & inhibitors
  • DNA-Binding Proteins / physiology*
  • Drug Resistance, Neoplasm
  • Gene Expression Profiling
  • Head and Neck Neoplasms / drug therapy*
  • Head and Neck Neoplasms / metabolism
  • Head and Neck Neoplasms / pathology
  • Humans
  • Immediate-Early Proteins / antagonists & inhibitors
  • Immediate-Early Proteins / physiology*
  • Molecular Sequence Data
  • Oligonucleotide Array Sequence Analysis
  • Proteins / metabolism
  • Tumor Cells, Cultured


  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Butyrate Response Factor 1
  • DNA-Binding Proteins
  • Immediate-Early Proteins
  • Proteins
  • ZFP36L1 protein, human
  • CASP3 protein, human
  • Caspase 3
  • Caspases
  • Cisplatin