Paclitaxel/Taxol sensitivity in human renal cell carcinoma is not determined by the p53 status

Cancer Lett. 2005 May 26;222(2):165-71. doi: 10.1016/j.canlet.2004.09.045. Epub 2004 Nov 10.

Abstract

In this study, we analyzed the role of the p53 status for paclitaxel/Taxol sensitivity in renal cell carcinomas (RCCs) of the clear cell type. Using immunohistochemistry, nuclear p53 accumulation could not be correlated to the paclitaxel/Taxol sensitivity. DNA sequencing detected a p53 gene mutation in two out of eight RCC cell lines, i.e. in exon 8 (cell line clearCa-6), and in exon 9 (cell line clearCa-5). No correlation, however, was found between the p53 status of our RCC cell lines and their paclitaxel/Taxol sensitivity as indicated by the IC50 values. However, paclitaxel-induced growth inhibition in paclitaxel-sensitive RCC cell lines was accompanied by an increase in apoptosis, irrespective of their p53 status. Although CD95 up-regulation was observed in renal cell carcinoma with wild-type p53 upon paclitaxel treatment, paclitaxel-induced apoptosis itself is triggered independently from the CD95 system. In conclusion, the p53 status cannot predict paclitaxel/Taxol sensitivity in RCC cell lines of the clear cell type.

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / pathology*
  • DNA Mutational Analysis
  • DNA, Neoplasm
  • Drug Resistance, Neoplasm
  • Genes, p53*
  • Humans
  • Immunohistochemistry
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / pathology*
  • Paclitaxel / pharmacology*
  • Sequence Analysis, DNA
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents, Phytogenic
  • DNA, Neoplasm
  • Paclitaxel