Polyamine analogues down-regulate estrogen receptor α expression in human breast cancer cells

Yi Huang, Judith C. Keen, Allison Pledgie, Laurence J. Marton, Tao Zhu, Saraswati Sukumar, Ben Ho Park, Brian Blair, Keith Brenner, Robert A. Casero, Nancy E. Davidson

Research output: Contribution to journalArticlepeer-review

Abstract

The critical role of polyamines in cell growth has led to the development of a number of agents that interfere with polyamine metabolism including a novel class of polyamine analogues, oligoamines. Here we demonstrate that oligoamines specifically suppress the mRNA and protein expression of estrogen receptor α (ERα) and ERα target genes in ER-positive human breast cancer cell lines, whereas neither ERβ nor other steroid hormonal receptors are affected by oligoamines. The constitutive expression of a cytomegalovirus promoter-driven exogenous ERα in ER-negative MDA-MB-231 human breast cancer cells was not altered by oligoamines, suggesting that oligoamines specifically suppress ERα transcription rather than affect mRNA or protein stability. Further analysis demonstrated that oligoamines disrupted the DNA binding activity of Sp1 transcription factor family members to an ERα minimal promoter element containing GC/CA-rich boxes. Treatment of MDA-MB-231 cells with the JNK-specific inhibitor SP600125 or expression of the c-Jun dominant negative inhibitor TAM67 blocked the oligoamine-activated JNK/c-Jun pathway and enhanced oligoamine-inhibited ERα expression, suggesting that AP-1 is a positive regulator of ERα expression and that oligoamine-activated JNK/AP-1 activity may antagonize the down-regulation of ERα induced by oligoamines. Taken together, these results suggest a novel antiestrogenic mechanism for specific polyamine analogues in human breast cancer cells.

Original languageEnglish (US)
Pages (from-to)19055-19063
Number of pages9
JournalJournal of Biological Chemistry
Volume281
Issue number28
DOIs
StatePublished - Jul 14 2006

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Polyamine analogues down-regulate estrogen receptor α expression in human breast cancer cells'. Together they form a unique fingerprint.

Cite this