Lessons learned from BRCA1 and BRCA2

L. Zheng, S. Li, T. G. Boyer, W. H. Lee

Research output: Contribution to journalReview article

Abstract

BRCA1 and BRCA2 are breast cancer susceptibility genes. Mutations within BRCA1 and BRCA1 are responsible for most familial breast cancer cases. Targeted deletion of Brca1 or Brca2 in mice has revealed an essential function for their encoded products, BRCA1 and BRCA2, in cell proliferation during embryogenesis. Mouse models established from conditional expression of mutant Brca1 alleles develop mammary gland tumors, providing compelling evidence that BRCA1 functions as a breast cancer suppressor. Human cancer cells and mouse cells deficient in BRCA1 or BRCA2 exhibit radiation hypersensitivity and chromosomal abnormalities, thus revealing a potential role for both BRCA1 and BRCA2 in the maintenance of genetic stability through participation in the cellular response to DNA damage. Functional analyses of the BRCA1 and BRCA2 gene products have established their dual participation in transcription regulation and DNA damage repair. Potential insight into the molecular basis for these functions of BRCA1 and BRCA2 has been provided by studies that implicate these two tumor suppressors in both the maintenance of genetic stability and the regulation of cell growth and differentiation.

Original languageEnglish (US)
Pages (from-to)6159-6175
Number of pages17
JournalOncogene
Volume19
Issue number53
DOIs
StatePublished - Dec 11 2000
Externally publishedYes

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Keywords

  • BRCA1
  • BRCA2
  • Breast cancer
  • DNA damage repair
  • Transcription regulation
  • Tumor suppressor

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Zheng, L., Li, S., Boyer, T. G., & Lee, W. H. (2000). Lessons learned from BRCA1 and BRCA2. Oncogene, 19(53), 6159-6175. https://doi.org/10.1038/sj.onc.1203968