Dominant-negative activity of a Brca1 truncation mutant: effects on proliferation, tumorigenicity in vivo, and chemosensitivity in a mouse ovarian cancer cell line.
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.
Sylvain
Valerie
V
Laboratoire d'Oncologie Moleculaire, Centre Jean Perrin, BP 392, 63 011 Clermont-Ferrand Cedex 1, France.
Lafarge
Stephane
S
Bignon
Yves-Jean
YJ
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D019313:BRCA1 Protein / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D017931:DNA Primers / Q000737:chemistry; D004273:DNA, Neoplasm / Q000378:metabolism; D004351:Drug Resistance; D005260:Female; D005799:Genes, Dominant; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016133:Polymerase Chain Reaction; D012334:RNA, Neoplasm / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000473:pathology
D000970:Antineoplastic Agents; D019313:BRCA1 Protein; D017931:DNA Primers; D004273:DNA, Neoplasm; D012334:RNA, Neoplasm