Talk abstracts
Talk on Wednesday 09:00-09:15am submitted by Andrea R. Patterson
Persistent impact of chronic endocrine disruption upon estrogen signaling
Andrea R. Patterson (Department of Molecular Genetics, The James Comprehensive Cancer Center, The Ohio State University), Xiaokui Mo (Center for Bioinformatics, The Ohio State University Wexner Medical Center), Ali Shapiro (Department of Molecular Genetics, The James Comprehensive Cancer Center, The Ohio State University), Karen E. Wernke (Department of Molecular Genetics, The Ohio State University), Trevor K. Archer (4National Institute of Environmental Health Sciences, Laboratory of Molecular Carcinogenesis, Research Triangle Park, NC), Craig J. Burd (Department of Molecular Genetics, The James Comprehensive Cancer Center, The Ohio State University)
Abstract:
The pervasive nature of estrogenic industrial and dietary compounds is a growing health concern linked to cancer, obesity, and neurological disorders. Prior analyses of endocrine disruptor action have focused primarily on the short-term consequences of exposure. However, these studies are unlikely to reflect the consequences of constant exposures common to industrialized countries. Here, we examined the global effects of long-term endocrine disruption on gene transcription and estrogen signaling. Estrogen-dependent breast cancer cell lines were chronically treated with physiologically relevant levels of bisphenol A or genistein for more than 70 passages. Microarray analysis demonstrated global reprogramming of the transcriptome when compared to a similarly cultured control cell line. Estrogen responsive targets showed diminished expression in both the presence and absence of estrogen. ER recruitment, H3K4 monomethylation, and DNase accessibility were reduced at nearby response elements. Based upon these observations, we investigated the potential of long-term EDC exposure to initiate persistent transcriptional reprogramming. Culture of chronically exposed cell lines in the absence of the endocrine disruptors did not reverse many of the signaling defects that accumulated during treatment. Taken together, these data demonstrate that chronic exposure to endocrine disrupting compounds can permanently alter physiological hormone signaling.
Keywords: Estrogen receptor, Epigenetics, Endocrine disruptor