アクティブボード・2014年 2月
・・・・・2014年 2月 8日更新・・・・・
研究発表を行った学会;
・第36回日本分子生物学会
2013年12月 3日〜 6日(神戸)
タイトル;Epigenetic regulation of the ESR1 locus during estrogen deprivation in breast cancer.
発表者;Mohamed Osama Abdalla 氏
(熊本大学 発生医学研究所 細胞医学分野)
Abstract;
Estrogen Receptor (ER) alpha is a nuclear receptor that mediates action of estrogen. It is a key molecule that drives cell proliferation in breast cancers. Endocrine therapy that targets ER signaling is effective in majority of ER positive breast tumor patients; however, it is a problem that resistance to the therapy develops later on with regrowth of original tumors. Human breast adenocarcinoma cell line MCF7 cells express ER at high level under Long Term Estrogen Deprivation (LTED), and provide a good model for endocrine therapy resistance. Higher ordered epigenetic regulation of nuclear structures and long range chromatin interactions between distal sites plays a critical role in genome functions in various aspects of biology including cancer. We investigated several epigenetic regulations in the LTED cells. Our immunofluorescent analysis with anti-RNA polymerase II antibodies showed significant changes in distribution of transcription factories in the nuclei of LTED cell. Our FISH data using multiple BAC clones corresponding to the ER gene locus (ESR1) showed enlarged RNA foci in the nuclei of LTED cells. We also investigated long range chromatin interactions of the ESR1 locus using Circular Chromosomal Conformation Capture-Seq (4C-seq) technology. Annotation of interacting regions revealed interaction ofESR1 with regions known to be disturbed in breast cancer especially on chromosomes 6, 17, and 20. Our work aims to understand the role of regions interacting with ESR1 during acquaintance of endocrine resistance in breast tumor.