Expression of an amino-terminal BRCA1 deletion mutant causes a dominant growth inhibition in MCF10A cells

Fanglei You, Natsuko Chiba, Chikashi Ishioka, Jeffrey D. Parvin

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

Expression of deletion mutants of the breast and ovarian cancer-specific tumor suppressor protein, BRCA1, in the mammary epithelial cell line MCF10A revealed a powerful growth suppressive effect by a mutant that has the amino-terminal 302 amino acids deleted (ΔN-BRCA1). The growth suppression is associated with an increase in apoptosis and amplification in centrosome number. The growth inhibitory effect of ΔN-BRCA1 was not observed in cervical epithelial HeLa cells, suggesting that the phenotypes of BRCA1 mutant proteins differ depending on the cell line being tested. An internal domain, including BRCA1 residues 303-1292, caused the suppression of MCF10A cell growth, and the amino terminus of BRCA1 autoinhibited the growth suppression. Single point mutations that disrupted the amino-terminal RING domain of BRCA1 caused significant suppression of growth in MCF10A cells. These results suggest that the proper function of the RING domain, likely to be ubiquitin ligase function, is important in regulating the growth of the mammary epithelial cell line and in autoregulating the powerful internal growth-inhibiting domain of the BRCA1 tumor suppressor.

Original languageEnglish
Pages (from-to)5792-5798
Number of pages7
JournalOncogene
Volume23
Issue number34
DOIs
Publication statusPublished - 2004 Jul 29

Keywords

  • Apoptosis
  • BRCA1
  • Centrosomes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Fingerprint

Dive into the research topics of 'Expression of an amino-terminal BRCA1 deletion mutant causes a dominant growth inhibition in MCF10A cells'. Together they form a unique fingerprint.

Cite this