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DAX-1 expression is regulated during mammary epithelial cell differentiation
Luisa A Helguero1, Malin Hedengran Faulds, Carola Förster
1Department of Biosciences and Nutrition, Karolinska Institutet NOVUM, SE-141 86 Huddinge, Sweden.
Endocrinology
|April 22, 2006
Summary
DAX-1 (dosage-sensitive sex reversal/adrenal hypoplasia congenita critical region on the X chromosome) expression and localization change during mouse mammary cell differentiation. DAX-1 also inhibits estrogen receptor activity in these cells.
Area of Science:
- Cell Biology
- Endocrinology
- Molecular Biology
Background:
- DAX-1 (dosage-sensitive sex reversal/adrenal hypoplasia congenita critical region on the X chromosome) is a gene implicated in development.
- Its role in mammary epithelial cell differentiation and hormonal regulation is not fully understood.
Purpose of the Study:
- To investigate the regulation of DAX-1 expression and subcellular localization during mouse mammary epithelial cell differentiation.
- To examine the hormonal regulation of DAX-1 in the mouse mammary gland.
- To determine the influence of DAX-1 on estrogen receptor activity.
Main Methods:
- Western blotting and quantitative real-time PCR to detect DAX-1 expression.
- Confocal microscopy to assess subcellular localization.
- Luciferase reporter assays and quantitative real-time PCR to evaluate estrogen receptor activity.
Main Results:
- DAX-1 expression increased upon epidermal growth factor (EGF) withdrawal and induced differentiation in HC11 cells.
- DAX-1 levels increased with differentiation, showing a shift from nuclear to cytoplasmic localization in vivo.
- DAX-1 inhibited estrogen response element-reporter and ER-regulated gene expression induced by estrogens.
Conclusions:
- DAX-1 expression is upregulated during mammary epithelial cell differentiation.
- DAX-1 exhibits dynamic subcellular localization changes during mammary gland development and lactation.
- DAX-1 negatively modulates estrogen receptor transcriptional activity in mammary epithelial cells.