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

Publication ,  Journal Article
Chen, Z; Lan, X; Wu, D; Sunkel, B; Ye, Z; Huang, J; Liu, Z; Clinton, SK; Jin, VX; Wang, Q
Published in: Nat Commun
September 16, 2015

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 unfavourable 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.

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Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

September 16, 2015

Volume

6

Start / End Page

8323

Location

England

Related Subject Headings

  • Tyramine
  • Triple Negative Breast Neoplasms
  • Reverse Transcriptase Polymerase Chain Reaction
  • Response Elements
  • Receptors, Glucocorticoid
  • Paclitaxel
  • Ligands
  • Humans
  • Glucocorticoids
  • Gene Expression Regulation, Neoplastic
 

Citation

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Chen, Z., Lan, X., Wu, D., Sunkel, B., Ye, Z., Huang, J., … Wang, Q. (2015). Ligand-dependent genomic function of glucocorticoid receptor in triple-negative breast cancer. Nat Commun, 6, 8323. https://doi.org/10.1038/ncomms9323
Chen, Zhong, Xun Lan, Dayong Wu, Benjamin Sunkel, Zhenqing Ye, Jiaoti Huang, Zhihua Liu, Steven K. Clinton, Victor X. Jin, and Qianben Wang. “Ligand-dependent genomic function of glucocorticoid receptor in triple-negative breast cancer.Nat Commun 6 (September 16, 2015): 8323. https://doi.org/10.1038/ncomms9323.
Chen Z, Lan X, Wu D, Sunkel B, Ye Z, Huang J, et al. Ligand-dependent genomic function of glucocorticoid receptor in triple-negative breast cancer. Nat Commun. 2015 Sep 16;6:8323.
Chen, Zhong, et al. “Ligand-dependent genomic function of glucocorticoid receptor in triple-negative breast cancer.Nat Commun, vol. 6, Sept. 2015, p. 8323. Pubmed, doi:10.1038/ncomms9323.
Chen Z, Lan X, Wu D, Sunkel B, Ye Z, Huang J, Liu Z, Clinton SK, Jin VX, Wang Q. Ligand-dependent genomic function of glucocorticoid receptor in triple-negative breast cancer. Nat Commun. 2015 Sep 16;6:8323.

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

September 16, 2015

Volume

6

Start / End Page

8323

Location

England

Related Subject Headings

  • Tyramine
  • Triple Negative Breast Neoplasms
  • Reverse Transcriptase Polymerase Chain Reaction
  • Response Elements
  • Receptors, Glucocorticoid
  • Paclitaxel
  • Ligands
  • Humans
  • Glucocorticoids
  • Gene Expression Regulation, Neoplastic