Expression of Brca1 is associated with terminal differentiation of ectodermally and mesodermally derived tissues in mice

Timothy F Lane*, Chuxia Deng, Ari Elson, Myung S. Lyu, Christine A. Kozak, Philip Leder

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

190 Scopus citations

Abstract

We have isolated genomic and cDNA clones of Brca1, a mouse homolog of the recently cloned breast cancer-associated gene, BRCA1. Brca1 encodes an 1812- amino-acid protein with a conserved zinc finger domain and significant homology to the human protein. Brca1 maps to Chromosome 11 within a region of conserved synteny with human chromosome 17, consistent with the mapping of the human gene to 17q21. Brca1 transcripts are expressed in a variety of cultured cells but reveal a specific and dynamic expression pattern during embryonic development. For example, expression is observed first in the otic vesicle of embryonic day 9.5 (E9.5) embryos. This expression diminishes and is replaced by expression in the neuroectoderm at E10.5. By E11-12.5, higher levels are observed in differentiating keratinocytes and in whisker pad primordia. Transcripts also become evident in epithelial cells of the E14-17 kidney. Brca1 expression occurs in differentiating epithelial cells of several adult organs as well, suggesting a general role in the functional maturation of these tissues. Consistent with this, Brca1 transcripts are expressed in both alveolar and ductal epithelial cells of the mammary gland. During pregnancy, there is a large increase in Brca1 mRNA in mammary epithelial cells, an increase that parallels their functional differentiation. Because high rates of breast cancer are associated with loss of BRCA1 in humans, it is possible that this gene provides an important growth regulatory function in mammary epithelial cells. In addition, increased transcription of mammary Brca1 during pregnancy might contribute, in part, to the reduced cancer risk associated with exposure to pregnancy and lactation.

Original languageEnglish (US)
Pages (from-to)2712-2722
Number of pages11
JournalGenes and Development
Volume9
Issue number21
DOIs
StatePublished - Nov 1 1995

Keywords

  • Brca1 expression
  • Ring finger
  • embryomic development
  • mammary gland
  • mouse homolog
  • terminal differentiation
  • transcription

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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