Hormonal Regulation of Mammary Gland Development and Breast Cancer
Abstract
Our laboratory is interested in studying the mechanisms by which lactogenic hormones regulate Beta-casein gene expression and how alterations in the levels of these hormones may function in the growth promotion of breast tumors. To understand the role of C/EBPBeta, STAT5, GR and comodulatory factors in hormonally-regulated chromatin remodeling at the Beta-casein promoter and enhancer, we have performed RNA analysis and chromatin immunoprecipitation assays in HC11 mammary epithelial cells and the mouse mammary gland, At present, we have developed the ChIP assay and optimized it for use in HC11 cells and successfully extended these studies to lactating mammary gland tissue and liver. We have been able to demonstrate rapid acetylation at both the promoter and the enhancer regions after stimulation of cells with prolactin and hydrocortisone. We used antibodies to different transcription factors in modified ChIP assays and employed real time PCR for quantitative analysis following treatment with prolactin alone, hydrocortisone alone, or both hormones in HC11 cells. More recently, we have been able to demonstrate the chromatin association of GR with C/EBPBeta and recruitment of C/EBPBeta in chromatin remodeling of HC11 cells treated with both prolactin and hydrocortisone. We are currently investigating the kinetics of C/EBPBeta binding at the Beta-casein gene promoter and enhancer. These studies should help elucidate the mechanisms by which hormonal regulated signal transduction pathways regulate mammary-specific gene expression.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2004
- Accession Number
- ADA435276
Entities
People
- Jeffrey M. Rosen
- Wa Xian
Organizations
- Baylor College of Medicine