p53 Mutation and Cyclin D1 Amplification Correlate With Cisplatin Sensitivity in Xenografted Human Squamous Cell Carcinomas From Head and Neck

Acta Oncol. 2006;45(3):300-5. doi: 10.1080/02841860600547380.

Abstract

To investigate the response of tumour growth to cisplatin treatment, in relation to p53 mutation and cyclin D1 dysregulation on DNA and protein level, biopsies from seven xenografted human squamous cell carcinomas from the head and neck were analysed with immunohistochemistry for p53 expression and cyclin D1 expression. Polymerase chain reaction-singlestranded conformation polymorphism was used to determine p53 mutations. Fluorescence in situ hybridization was performed to analyse cyclin D1 amplification. The mice were injected i.p. with NaCl (controls) or cisplatin. After injection the tumour volume were measured. The inhibition of tumour growth by cisplatin was defined as the area under the growth curves, and compared with the growth curves of the tumours in the control group. Xenografts with p53 mutation showed significantly higher resistance to cisplatin (p < 0.001) and also tumours with cyclin D1 amplification showed significantly higher resistance (p < 0.001).

Publication types

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

MeSH terms

  • Animals
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / genetics
  • Cheek / pathology
  • Cisplatin / therapeutic use*
  • Cyclin D1 / genetics*
  • Cyclin D1 / metabolism
  • Drug Resistance, Neoplasm*
  • Flow Cytometry
  • Gene Amplification*
  • Gingival Neoplasms / drug therapy
  • Head and Neck Neoplasms / drug therapy*
  • Head and Neck Neoplasms / genetics
  • Humans
  • Laryngeal Neoplasms / drug therapy
  • Mice
  • Mouth Neoplasms / drug therapy
  • Mutation
  • Neoplasms, Unknown Primary / drug therapy
  • Statistics as Topic
  • Tumor Suppressor Protein p53 / genetics*
  • Tumor Suppressor Protein p53 / metabolism
  • Xenograft Model Antitumor Assays*

Substances

  • Tumor Suppressor Protein p53
  • Cyclin D1
  • Cisplatin