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Series GSE60517 Query DataSets for GSE60517
Status Public on Dec 31, 2015
Title Drug specific epigenetic reprogramming leads to increased cellular invasion in ERα positive breast cancer via de novo cholesterol biosynthesis.
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Endocrine therapy resistance remains a critical problem in the treatment of estrogen receptor alpha (ERα) breast cancer. Endocrine therapies target ERα via different modes of action. Drug resistance involves drug specific remodeling of the transcriptional and regulatory landscape. Using epigenomics and transcriptomics, we demonstrate that resistance to aromatase inhibitors (AI) induces phenotypical changes through epigenetic activation of cholesterol biosynthesis (CB) and keratin 80. Epigenetic activation is stable and involves both large topological domains and punctuated activation of single enhancers and super-enhancers. Specialized cancer cells expressing high levels of keratin 80 lead invasion through the extracellular matrix. Strikingly, we demonstrate that anti-cholesterol strategies can effectively arrest breast cancer invasion. Our work identifies a robust strategy to target resistant invasive breast cancer.
Overall design All cell lines were grown in their respective media until they reached 70% confluency. Specifically, MCF7 were grown in DMEM+10% FBS and 1% Pen-Sprep-Glutamine. MCF7T as MCF7 with the addition of 100nM Tamoxifen. MCF7F as MCF7 with the addition of 100nM Fulvestrant. LTED were grown in DMEM without phenol + 10% DCS-FBS and1% Pen-Sprep-Glutamine. LTEDT as LTED with the addition of 100nM Tamoxifen. LTEDF as LTED with the addition of 100nM of Fulvestrant. All chemicals are purchased from Sigma. ChIP-seq was performed using Illumina methodology.
Contributor(s) Magnani L
Citation(s) 26610607
Submission date Aug 19, 2014
Last update date May 15, 2019
Contact name Luca Magnani
Organization name Imperial College London
Department Surgery and Cancer
Lab Magnani's Lab
Street address DuCane road
City London
ZIP/Postal code W120NN
Country United Kingdom
Platforms (2)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
Samples (10)
GSM1481570 H3K27ac MCF7
GSM1481571 H3K27ac MCF7T
GSM1481572 H3K27ac MCF7F
BioProject PRJNA259193
SRA SRP045706

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Supplementary file Size Download File type/resource
GSE60517_RAW.tar 2.0 Gb (http)(custom) TAR (of BED, WIG)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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