Transcriptomics,Genomics

Dataset Information

307

Ligand-dependent genomic function of glucocorticoid receptor in triple-negative breast cancer


ABSTRACT: Glucocorticoids (GC) have been widely used as coadjuvants in the treatment of solid tumors, but GC treatment may be associated with poor pharmacotherapeutic response and/or prognosis. The genomic action of GC in these tumors is largely unknown. Here we find that dexamethasone (Dex, a synthetic GC) regulated genes in triple-negative breast cancer (TNBC) cells are associated with drug resistance. Importantly, these GC-regulated genes are aberrantly expressed in TNBC patients and associated with unfavorable clinical outcomes. Interestingly, in TNBC cells, Compound A (CpdA, a selective GR modulator) only regulates a small number of genes not involved in carcinogenesis and therapy resistance. Mechanistic studies using a ChIP-exo approach reveal that Dex- but not CpdA-liganded glucocorticoid receptor (GR) binds to a single glucocorticoid response element (GRE), which drives the expression of pro-tumorigenic genes. Our data suggest that development of safe coadjuvant therapy should consider the distinct genomic function between Dex- and CpdA-liganded GR. To study GR-regulated genes and define GRE in human genome, RNA-seq and GR ChIP-exo are performed in MDA-MB-231 cells before/after dex and CpdA stimulation. Each experiment includes two replicates.

ORGANISM(S): Homo sapiens  

SUBMITTER: Zhong Chen   Xun Lan  Qianben Wang 

PROVIDER: E-GEOD-56022 | ArrayExpress | 2015-09-18

SECONDARY ACCESSION(S): SRP040300GSE56022PRJNA242236

REPOSITORIES: GEO, ArrayExpress, ENA

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Publications

Ligand-dependent genomic function of glucocorticoid receptor in triple-negative breast cancer.

Chen Zhong Z   Lan Xun X   Wu Dayong D   Sunkel Benjamin B   Ye Zhenqing Z   Huang Jiaoti J   Liu Zhihua Z   Clinton Steven K SK   Jin Victor X VX   Wang Qianben Q  

Nature communications 20150916


Glucocorticoids (GCs) have been widely used as coadjuvants in the treatment of solid tumours, but GC treatment may be associated with poor pharmacotherapeutic response or prognosis. The genomic action of GC in these tumours is largely unknown. Here we find that dexamethasone (Dex, a synthetic GC)-regulated genes in triple-negative breast cancer (TNBC) cells are associated with drug resistance. Importantly, these GC-regulated genes are aberrantly expressed in TNBC patients and are associated with  ...[more]

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