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Yin Yang 1 positively regulates BRCA1 and inhibits mammary cancer formation

M-H Lee1, T Lahusen, R-H Wang

  • 1Genetics of Development and Disease Branch, 10/9N105, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Oncogene
|June 14, 2011
PubMed

Insights

Yin Yang 1 (YY1) transcription factor significantly boosts breast cancer gene 1 (BRCA1) expression. This discovery links YY1 to BRCA1 regulation and offers insights into human breast cancer development.

Area of Science:

  • Molecular Biology
  • Genetics
  • Oncology

Background:

  • Reduced expression of breast cancer-associated gene 1 (BRCA1) is common in sporadic breast cancers.
  • The mechanisms driving this reduced BRCA1 expression are not fully understood.

Purpose of the Study:

  • To identify transcription factors regulating BRCA1 expression.
  • To investigate the role of Yin Yang 1 (YY1) in BRCA1 regulation and its potential link to breast cancer etiology.

Main Methods:

  • Screened 92 known transcription factors for their ability to regulate the BRCA1 promoter.
  • Utilized reporter assays, gene expression analysis, cell proliferation assays, and xenograft tumor models.
  • Correlated YY1 and BRCA1 expression in human breast cancer samples and tissue arrays.

Main Results:

  • Yin Yang 1 (YY1) demonstrated significant transactivation of the BRCA1 promoter.
  • Overexpression of YY1 increased BRCA1 and its downstream gene expression.
  • YY1 overexpression inhibited cancer cell proliferation, foci formation, and tumor growth in vivo.
  • A significant positive correlation was observed between YY1 and BRCA1 expression levels in human breast cancer tissues.

Conclusions:

  • YY1 is identified as a key regulator of BRCA1 expression.
  • YY1's role in regulating BRCA1 suggests a potential causal link to the molecular mechanisms of human breast cancer.

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