|COOKIES: By using this website you agree that we can place Google Analytics Cookies on your device for performance monitoring.|
Mechanisms of Estrogen Receptor Transcription in Breast Cancer
If you have a question about this talk, please contact Mala Jayasundera.
Estrogen Receptor (ER) is the defining feature of luminal breast cancers, where is functions as a transcription factor. The traditional view of ER getting recruited to promoters of target genes is too simplistic. The recent discovery of ER-DNA interaction regions from ER+ breast cancer cell lines has revealed that ER rarely associates with promoter regions of target genes and instead associates with enhancer elements significant distances from the target genes. The genomic mapping of ER binding events also revealed the enrichment of DNA motifs for Forkhead factors. The Forkhead protein FOXA1 (HNF3a) was subsequently shown to bind to ~half of the ER binding events in the genome and was required for ER to maintain interaction with DNA . We have extended on these findings to map ER binding events in primary breast cancers and distant metastases. We find context dependent ER cis-regulatory elements (cistromes) that give insight into underlying transcriptional networks. These differential ER binding profiles correlate with clinical response in ER+ breast cancers. We experimentally explore the binding dynamics between drug sensitive and resistant contexts and identify properties that govern ER binding differences. These data suggest that ER-DNA interactions are dynamic and can be modulated by changes in FOXA1 . We are currently exploring mechanisms that mediate FOXA1 -DNA interactions, in order to better understand ER transcriptional activity in breast cancer biology.
This talk is part of the Cambridge Oncology Seminar Series series.
This talk is included in these lists:
Note that ex-directory lists are not shown.
Other listsOpen Cambridge talks Mr Keynes and the Moderns Nineteenth-Century Epic
Other talksConsistency of Quine's NF using nominal techniques Weak and 'Very Weak' Solutions for Euler and Navier-Stokes Equations in 2 and 3 Dimensions LARMOR LECTURE - title to be confirmed Beating Malaria 2015 Designing drugs at the 5HT1B serotonin receptor: from Migraine to Pulmonary Hypertension Exploring the Extreme Climates of Giant Planets