Dominant-negative activity of a Brca1 truncation mutant: effects on proliferation, tumorigenicity in vivo, and chemosensitivity in a mouse ovarian cancer cell line

Int J Oncol. 2002 Apr;20(4):845-53.


In order to generate an in vitro mouse model for the study of human ovarian cancers, we compared the effects of a truncated Brca1 mutant expression on cellular phenotype with those of a full-length sense and antisense Brca1 expression in the ID-8 mouse epithelial ovarian cancer cell line. The examined cellular processes include proliferation, tumorigenicity in syngeneic mice in vivo and sensitivity/resistance to several cytotoxic drugs. We found that the expression of a spontaneous truncated Brca1 mutant in ID-8 cells which contain two endogenous wild-type Brca1 alleles led to a dominant-negative effect of Brca1, demonstrated by an increase in tumorigenicity in vivo and in chemosensitivity. Expression of a truncated Brca1 mutant in a mouse epithelial ovarian cancer cell line could thus provide a powerful in vitro model for the study of human BRCA1-related ovarian tumorigenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Apoptosis
  • BRCA1 Protein / genetics*
  • BRCA1 Protein / metabolism
  • Blotting, Western
  • DNA Primers / chemistry
  • DNA, Neoplasm / metabolism
  • Drug Resistance
  • Female
  • Genes, Dominant
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Mutation*
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology*
  • Polymerase Chain Reaction
  • RNA, Neoplasm / metabolism
  • Transfection
  • Tumor Cells, Cultured / metabolism
  • Tumor Cells, Cultured / pathology


  • Antineoplastic Agents
  • BRCA1 Protein
  • DNA Primers
  • DNA, Neoplasm
  • RNA, Neoplasm