Expression of p53-family members and associated target molecules in breast cancer cell lines in response to vincristine treatment

Biochem Pharmacol. 2002 May 1;63(9):1609-17. doi: 10.1016/s0006-2952(02)00917-6.

Abstract

As the antimitotic agent vincristine (VCR) has been reported to induce a weak p53 response in some studies, we hypothesised that p73 and p63, the recently described p53 homologues, may replace p53 in triggering apoptosis or cell cycle arrest effectors in VCR-treated cell lines. To address this issue, we measured p53, p73 and p63 mRNA and protein levels in two VCR-treated breast cancer cell lines, one p53-proficient (MCF7) and the other p53-deficient (MDA-MB157). We found an increase of p53 mRNA and protein levels in VCR-treated MCF7 cells, while, as expected, no p53 protein was detected in VCR-treated MDA-MB157 cells. Surprisingly, the p73 mRNA and protein expression levels decreased in both cell lines during VCR treatment, whereas p63 protein levels remained unchanged. In both cell lines, up-regulations of the canonical p53-target genes, such as p21 and GADD45, were consistently observed. We conclude that, in response to VCR treatment: (1) p53 is markedly induced in MCF7 cells, with the same extent than after DNA damaging drugs treatments; and (2) p63 is not involved, while p73 expression is down-regulated regardless of the p53 status of the cell lines. Our results therefore suggest the involvement of a fourth member of the p53 gene family, or the use of another pathway able to trigger canonical p53-target genes in response to VCR in p53-deficient cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Genes, Tumor Suppressor
  • Humans
  • Membrane Proteins*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Transcription Factors
  • Tumor Cells, Cultured
  • Tumor Protein p73
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*
  • Tumor Suppressor Proteins
  • Up-Regulation
  • Vincristine / pharmacology*

Substances

  • Antineoplastic Agents, Phytogenic
  • CKAP4 protein, human
  • DNA-Binding Proteins
  • Membrane Proteins
  • Nuclear Proteins
  • Phosphoproteins
  • TP63 protein, human
  • Trans-Activators
  • Transcription Factors
  • Tumor Protein p73
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins
  • p73 protein, human
  • Vincristine