Effects of p53-expressing adenovirus on the chemosensitivity and differentiation of anaplastic thyroid cancer cells

J Clin Endocrinol Metab. 1998 Jul;83(7):2516-22. doi: 10.1210/jcem.83.7.4984.


We investigated the p53 status and the ability of exogenous wildtype (wt) p53 to affect chemosensitivity in three anaplastic thyroid carcinoma cell lines (BHT-101, SW-1736, and KAT-4). All three cell lines had nonfunctional p53. Treatment with mitomycin C or adriamycin did not result in accumulation of p53 or induction of p21WAF1/CIP1 or Mdm-2 and did not cause Rb dephosphorylation. BHT-101 and KAT-4 cells had mutant p53. SW-1736 cells were functionally mutant because of marked down-regulation of wt p53 messenger ribonucleic acid, representing a novel mechanism of p53 dysfunction. Infection with a p53-expressing adenovirus (Ad-p53) induced high levels of p21 and Mdm-2 proteins. In BHT-101 cells, induction of p21 and Mdm-2 was evident 10 h after infection. In KAT-4 cells, induction of p21 and Mdm-2 was observed 1 day after infection, and continued to increase over the ensuing 24 h. SW-1736 cells demonstrated intermediate kinetics. Sensitivity to the cytotoxic effect of Ad-p53 paralleled the kinetics of p21/Mdm-2 induction. BHT-101 cells were most sensitive to killing by Ad-p53, with an IC50 of less than 2 multiplicity of infection; SW-1736 cells were intermediate in sensitivity; KAT-4 cells were resistant. All three cell lines became more sensitive to adriamycin after wt p53 expression, with a 10-fold decrease in IC50 values. The latter observation may make a combination of wt p53 and chemotherapeutic drugs an attractive modality for treating anaplastic thyroid cancer.

MeSH terms

  • Adenoviridae / genetics*
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma / drug therapy*
  • Carcinoma / virology
  • Cell Differentiation / physiology
  • Cisplatin / therapeutic use
  • DNA Damage
  • Doxorubicin / therapeutic use
  • Gene Expression Regulation, Viral / physiology*
  • Genes, p53*
  • Humans
  • Kinetics
  • Lac Operon
  • Thyroid Neoplasms / drug therapy*
  • Thyroid Neoplasms / pathology
  • Thyroid Neoplasms / virology
  • Tumor Cells, Cultured


  • Antineoplastic Agents
  • Doxorubicin
  • Cisplatin