Anti-proliferative actions of a synthetic REV-ERBα/β agonist in breast cancer cells

Yongjun Wang, Douglas Kojetin, Thomas P. Burris

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Abstract REV-ERBα and REV-ERBβ are nuclear receptors that are ligand-dependent transcriptional repressors. Heme is the natural ligand for these receptors, but several synthetic agonists and antagonists have been designed recently. The gene that encodes REV-ERBα, NR1D1, is closely associated with ERBB2, the gene that encodes the HER2 oncogene, which is amplified in HER2+ breast cancers. We examined the effect of a synthetic REV-ERB agonist, SR9011, on a range of estrogen receptor positive (ER+), ER-, HER2+, HER2- and triple negative breast cancer cell lines. We found that SR9011 suppressed proliferation of the breast cancer cell lines regardless of their ER or HER2 status. SR9011 had no effect on MCF10A cell proliferation. SR9011 appears to pause the cell cycle of the breast cancer cells prior to M phase. Cyclin A (CCNA2) was identified as a direct target gene of REV-ERB suggesting that suppression of expression of this cyclin by SR9011 may mediate the cell cycle arrest. These data indicate that synthetic REV-ERB ligands may hold utility in treatment of diseases associated with uncontrolled cellular proliferation such as cancer.

Original languageEnglish (US)
Article number12267
Pages (from-to)315-322
Number of pages8
JournalBiochemical Pharmacology
Volume96
Issue number4
DOIs
StatePublished - Aug 3 2015

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Cells
Breast Neoplasms
Genes
Ligands
Artificial Receptors
Cell Proliferation
Triple Negative Breast Neoplasms
erbB-2 Genes
Cyclin A
Cell Line
Cyclins
Cell proliferation
Cytoplasmic and Nuclear Receptors
Cell Cycle Checkpoints
Heme
Oncogenes
Estrogen Receptors
Cell Division
Cell Cycle
SR9011

Keywords

  • Cell cycle
  • Circadian rhythm
  • Heme
  • Nuclear receptor
  • Steroid receptor

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

Cite this

Anti-proliferative actions of a synthetic REV-ERBα/β agonist in breast cancer cells. / Wang, Yongjun; Kojetin, Douglas; Burris, Thomas P.

In: Biochemical Pharmacology, Vol. 96, No. 4, 12267, 03.08.2015, p. 315-322.

Research output: Contribution to journalArticle

Wang, Yongjun ; Kojetin, Douglas ; Burris, Thomas P. / Anti-proliferative actions of a synthetic REV-ERBα/β agonist in breast cancer cells. In: Biochemical Pharmacology. 2015 ; Vol. 96, No. 4. pp. 315-322.
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