Upregulation of ZNRD1 enhances cisplatin resistance in human esophageal cancer cells by regulation of ERCC1 and Bcl-2

Tumour Biol. 2008;29(3):188-94. doi: 10.1159/000146864. Epub 2008 Jul 22.

Abstract

Background/aims: The precise mechanism of the zinc ribbon domain-containing-1 (ZNRD1) gene on cisplatin resistance remains unclear. The aim of this study is to identify the gene expression profile and explore the role of these genes in ZNRD1-induced cisplatin resistance in esophageal cancer cells.

Methods: An expression vector with ZNRD1 was transfected into the EC109 cells, and then cDNA microarray analysis was performed to identify the gene expression profile. The sensitivity of transfected EC109 cells to cisplatin was evaluated using the MTT assay. RT-PCR and Western blots were performed to validate the differential expression of genes identified by cDNA microarray analysis.

Results: We identified 16 genes with significantly different expression levels between the transfected and control cells. The tolerance of EC109 cells to cisplatin was significantly enhanced by the upregulation of ZNRD1. Furthermore, the expression of excision repair cross-complementing-1 (ERCC1) and B-cell lymphoma-2 (Bcl-2) was significantly upregulated.

Conclusion: The ZNRD1 gene might be involved in the cisplatin resistance of EC109 cells by regulating the expression of ERCC1 and Bcl-2.

MeSH terms

  • Antineoplastic Agents / therapeutic use
  • Apoptosis
  • Cell Line, Tumor
  • Cisplatin / therapeutic use*
  • DNA Fragmentation
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Drug Resistance, Neoplasm / genetics
  • Endonucleases / metabolism*
  • Esophageal Neoplasms / drug therapy*
  • Esophageal Neoplasms / metabolism*
  • Esophageal Neoplasms / pathology
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Oligonucleotide Array Sequence Analysis
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Up-Regulation*

Substances

  • Antineoplastic Agents
  • DNA-Binding Proteins
  • POLR1H protein, human
  • Proto-Oncogene Proteins c-bcl-2
  • ERCC1 protein, human
  • Endonucleases
  • Cisplatin