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Status |
Public on May 01, 2013 |
Title |
Genome-wide reprogramming of the chromatin landscape underlies endocrine therapy resistance in breast cancer |
Organism |
Homo sapiens |
Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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Summary |
The estrogen receptor alpha (ERa) drives the growth of two-thirds of all breast cancers. Endocrine therapy impinges on estrogen-induced ERa activation to block tumor growth. However, half of ERa-positive breast cancers are tolerant or acquire endocrine therapy resistance. Here we demonstrate that breast cancer cells undergo genome-wide reprogramming of their chromatin landscape, defined by epigenomic maps and chromatin openness, as they acquire resistance to endocrine therapy. This reveals a role for the Notch pathway while excluding classical ERa signaling. In agreement, blocking Notch signaling, using gamma-secretase inhibitors, or targeting its downstream gene PBX1 abrogates growth of endocrine therapy-resistant breast cancer cells. Moreover Notch signaling through PBX1 directs a transcriptional program predictive of tumor outcome and endocrine therapy response.
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Overall design |
Comparing histone modifications (H3K4me2 and H3K36me3), chromatin openness (FAIRE) and PBX1 binding between endocrine therapy sensitive MCF7 and resistant MCF7-LTED cells.
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Contributor(s) |
Zhang X |
Citation(s) |
23576735 |
Submission date |
Apr 16, 2012 |
Last update date |
May 15, 2019 |
Contact name |
xiaoyang zhang |
E-mail(s) |
xiaoyang.zhang@dartmouth.edu
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Organization name |
Dartmouth Medical School
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Street address |
1 Medical Center Driver
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City |
Lebanon |
ZIP/Postal code |
03756 |
Country |
USA |
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Platforms (2) |
GPL9052 |
Illumina Genome Analyzer (Homo sapiens) |
GPL9115 |
Illumina Genome Analyzer II (Homo sapiens) |
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Samples (9)
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This SubSeries is part of SuperSeries: |
GSE39418 |
Genome-wide reprogramming of the chromatin landscape underlies endocrine therapy resistance in breast cancer |
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Relations |
BioProject |
PRJNA159579 |
SRA |
SRP012270 |