Growth retardation and tumour inhibition by BRCA1.
Inherited mutations in BRCA1 predispose to breast and ovarian cancer, but the role of BRCA1 in sporadic breast and ovarian cancer has previously been elusive. Here, we show that retroviral transfer of the wild-type BRCA1 gene inhibits growth in vitro of all breast and ovarian cancer cell lines tested, but not colon or lung cancer cells or fibroblasts. Mutant BRCA1 has no effect on growth of breast cancer cells; ovarian cancer cell growth is not affected by BRCA1 mutations in the 5' portion of the gene, but is inhibited by 3' BRCA1 mutations. Development of MCF-7 tumours in nude mice is inhibited when MCF-7 cells are transfected with wild-type, but not mutant, BRCA1. Most importantly, among mice with established MCF-7 tumours, peritoneal treatment with a retroviral vector expressing wild-type BRCA1 significantly inhibits tumour growth and increased survival.
Holt
J T
JT
Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2175, USA.
Thompson
M E
ME
Szabo
C
C
Robinson-Benion
C
C
Arteaga
C L
CL
King
M C
MC
Jensen
R A
RA
D000818:Animals; D019313:BRCA1 Protein; D002455:Cell Division / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005822:Genetic Vectors; D015674:Mammary Neoplasms, Animal / Q000235:genetics*; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics* / Q000502:physiology; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology; D014162:Transfection; D014407:Tumor Cells, Cultured
D019313:BRCA1 Protein; D009363:Neoplasm Proteins; D014157:Transcription Factors