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SUMMARY:Mechanisms of Estrogen Receptor Transcription in Breast Cancer - D
 r Jason Carroll\, CRUK Cambridge Research Institute
DTSTART:20121120T120000Z
DTEND:20121120T130000Z
UID:TALK40274@talks.cam.ac.uk
CONTACT:Mala Jayasundera
DESCRIPTION:Estrogen Receptor (ER) is the defining feature of luminal brea
 st cancers\, where is functions as a transcription factor. The traditional
  view of ER getting recruited to promoters of target genes is too simplist
 ic. The recent discovery of ER-DNA interaction regions from ER+ breast can
 cer cell lines has revealed that ER rarely associates with promoter region
 s of target genes and instead associates with enhancer elements significan
 t distances from the target genes. The genomic mapping of ER binding event
 s also revealed the enrichment of DNA motifs for Forkhead factors. The For
 khead 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 inter
 action with DNA. We have extended on these findings to map ER binding even
 ts in primary breast cancers and distant metastases. We find context depen
 dent ER cis-regulatory elements (cistromes) that give insight into underly
 ing transcriptional networks. These differential ER binding profiles corre
 late with clinical response in ER+ breast cancers. We experimentally explo
 re 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 F
 OXA1. We are currently exploring mechanisms that mediate FOXA1-DNA interac
 tions\, in order to better understand ER transcriptional activity in breas
 t cancer biology.
LOCATION:CRI Lecture Theatre\, Cambridge Research Institute
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