Establishment of an apoptosis-sensitive rat mammary carcinoma cell line with a mutation in the DNA-binding region of p53

Cancer Lett. 2006 Feb 8;232(2):279-88. doi: 10.1016/j.canlet.2005.02.043.

Abstract

Seven mammary carcinoma cell lines were established from 7,12-dimethylbenz[a]anthracene-induced tumors developed in a human c-Ha-ras transgenic rat. Without apoptotic stimuli, a large amount of p53 protein was detected in the C11 cell line (C11), whereas all cell lines expressed variable levels of the assayed death receptor/ligand, bcl-2 family and p53 cascade-related genes. The p53 gene in C11 had a mutation at codon 246, in the DNA-binding region of p53. Transcriptional activity of the mutant protein appeared to be lower than that of the wild-type p53. Despite the presence of p53 mutation, C11 was more sensitive to apoptosis triggered by etoposide, paclitaxel and staurosporine than the cell lines expressing wild-type p53. These data suggest that the apoptosis induced by intracellular injury occurs via the transcriptionally impaired mutant p53 in C11.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • Binding Sites
  • Cell Line, Tumor
  • DNA / metabolism*
  • Female
  • Genes, ras
  • Humans
  • MAP Kinase Signaling System
  • Mammary Neoplasms, Experimental / genetics*
  • Mammary Neoplasms, Experimental / pathology
  • Point Mutation*
  • Rats
  • Tumor Suppressor Protein p53 / genetics*
  • Tumor Suppressor Protein p53 / metabolism
  • bcl-X Protein / metabolism

Substances

  • Bcl2l1 protein, rat
  • Tumor Suppressor Protein p53
  • bcl-X Protein
  • DNA