Differentially expressed genes associated with CIS-diamminedichloroplatinum (II) resistance in head and neck cancer using differential display and CDNA microarray

Head Neck. 2003 Mar;25(3):187-93. doi: 10.1002/hed.10204.

Abstract

Background: The mechanism by which cancer cells become resistant to cis-Diamminedichloroplatinum (II) (cDDP) is not completely understood. To investigate the molecular markers involved in the cDDP resistance, we compared the gene expression profiles between a head and neck squamous cell carcinoma (HNSCC) line sensitive to cDDP and its cDDP-resistant variant.

Methods: Both a fluorescent differential display and a cDNA microarray analysis were applied to distinguish the gene profiles between KB, a human HNSCC line, and its cDDP-resistant variant (KB/cDDP). These results were confirmed by Northern blot analysis.

Results: One up-regulated gene, glycoprotein hormone alpha-subunit, and two down-regulated genes coding membrane proteins, human folate receptor and tumor-associated antigen L6, were identified in KB/cDDP cells.

Conclusions: Our findings suggest that development of the cDDP-resistant phenotype is accompanied by alternations of gene expression including a glycoprotein hormone and membrane proteins. These gene products could be new molecular markers for resistance to cDDP.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Northern
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / genetics*
  • Cell Survival / drug effects
  • Cisplatin / pharmacology*
  • DNA, Complementary / analysis*
  • Drug Resistance, Neoplasm / genetics*
  • Female
  • Gene Expression Regulation
  • Genetic Markers / genetics
  • Head and Neck Neoplasms / drug therapy
  • Head and Neck Neoplasms / genetics*
  • Humans
  • Male
  • Membrane Glycoproteins / genetics
  • Oligonucleotide Array Sequence Analysis
  • Pharmacogenetics
  • Phenotype
  • Polymerase Chain Reaction / methods
  • Sensitivity and Specificity
  • Tumor Cells, Cultured / drug effects
  • Up-Regulation

Substances

  • DNA, Complementary
  • Genetic Markers
  • Membrane Glycoproteins
  • Cisplatin