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Invited Speaker Abstracts

Abstract AL-1: AACR outstanding investigator award for breast cancer research: Understanding estrogen receptor transcription in breast cancer

JS Carroll
JS Carroll
University of Cambridge, Cambridge, United Kingdom
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DOI: 10.1158/0008-5472.SABCS13-AL-1 Published December 2013
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Abstracts: Thirty-Sixth Annual CTRC-AACR San Antonio Breast Cancer Symposium - Dec 10-14, 2013; San Antonio, TX

Abstract

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 explore ER and FoxA1 functional interactions in breast cancer, with a specific focus on changes in binding dynamics that occur during endocrine resistance. To this end, we have established transcription factor mapping approaches (ChIP-seq) in primary tumor material, to investigate differential ER/FoxA1 binding that occurs during tumor progression. We have functionally explored underlying factors that contribute to altered transcription factor binding and activity. In addition, we have recently established a method for rapid unbiased discovery of protein interacting complexes, which we have applied to discover ER associated proteins. We find an unexpected interaction between ER and progesterone receptor (PR) in ER+ breast cancer. We show that PR is a negative regulator of the ER complex, where it is important for modulating ER-DNA interactions and cellular growth. These findings help delineate the complexes that influence ER transcriptional activity and ultimately impinge on tumor progression and drug sensitivity.

Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr AL-1.

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Cancer Research: 73 (24 Supplement)
December 2013
Volume 73, Issue 24 Supplement
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Abstract AL-1: AACR outstanding investigator award for breast cancer research: Understanding estrogen receptor transcription in breast cancer
JS Carroll
Cancer Res December 15 2013 (73) (24 Supplement) AL-1; DOI: 10.1158/0008-5472.SABCS13-AL-1

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Abstract AL-1: AACR outstanding investigator award for breast cancer research: Understanding estrogen receptor transcription in breast cancer
JS Carroll
Cancer Res December 15 2013 (73) (24 Supplement) AL-1; DOI: 10.1158/0008-5472.SABCS13-AL-1
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Cancer Research Online ISSN: 1538-7445
Cancer Research Print ISSN: 0008-5472
Journal of Cancer Research ISSN: 0099-7013
American Journal of Cancer ISSN: 0099-7374

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