Hormonal Regulation of Mammary Gland Development and Breast Cancer

Download or read book Hormonal Regulation of Mammary Gland Development and Breast Cancer written by and published by . This book was released on 2005 with total page 21 pages. Available in PDF, EPUB and Kindle. Book excerpt: One of the principal objectives of our laboratory is to understand the mechanisms by which hormones and growth factors regulate normal mammary gland development, and how these same regulatory pathways become altered in breast cancer. Therefore, specific interest has been placed upon studying the mechanisms by which the lactogenic hormones regulate milk protein gene expression. CAAT/enhancer binding protein beta(C/EBP(beta)), Yin Yang-1 (YY-1), signal transducers and activators or transcription 5 (STAT5), and the glucocorticoid receptor (GR) have been shown to mediate the hormonal and developmental regulation of a beta-casein gene. However, the mechanism by which these transcription factors as well as coactivator proteins coordinately function to promote normal mammary gland development and breast cancer remains undefined. In this study we tested the dynamic of assembly and disassembly of Stat5, GR, C/EBPb and YY-1 at the hormonally activated b-casein promoter as well as at the recently identified mouse b-casein enhancer located 6kb upstream of the transcription start site. Using ChIP analysis we examined the recruitment of coactivator p300 and determined chromatin acetylation and deacetylation status upon hormone treatments. Finally, we established the time course of pol II and phospho-pol II accumulation at the promoter and enhancer sites. Collectively, these data suggest a model for the assembly of multi-protein complex at the b-casein regulatory regions that helps to understand how the signaling pathways regulated by lactogenic hormones and local growth factors are integrated in the nucleus.