Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

0

Drug specific epigenetic reprogramming leads to increased cellular invasion in ERα positive breast cancer via de novo cholesterol biosynthesis.


ABSTRACT: 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. 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.

ORGANISM(S): Homo sapiens

SUBMITTER: Luca Magnani 

PROVIDER: E-GEOD-60517 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

Similar Datasets

2018-01-12 | GSE100074 | GEO
2017-04-05 | E-MTAB-4426 | biostudies-arrayexpress
2018-01-12 | GSE100075 | GEO
2015-06-29 | E-GEOD-69893 | biostudies-arrayexpress
2015-06-29 | GSE69893 | GEO
2012-05-13 | E-GEOD-22533 | biostudies-arrayexpress
2012-05-14 | GSE22533 | GEO
2011-07-17 | E-GEOD-27444 | biostudies-arrayexpress
2016-06-01 | PXD004085 | Pride
2020-07-13 | PXD004648 | Pride