Journal article
Polyamine Analogues Down-regulate Estrogen Receptor α Expression in Human Breast Cancer Cells
The Journal of biological chemistry, Vol.281(28), pp.19055-19063
07/14/2006
DOI: 10.1074/jbc.M600910200
PMCID: PMC3623667
PMID: 16679312
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.
Details
- Title: Subtitle
- Polyamine Analogues Down-regulate Estrogen Receptor α Expression in Human Breast Cancer Cells
- Creators
- Yi Huang - Sidney Kimmel Comprehensive Cancer CenterJudith C. Keen - Sidney Kimmel Comprehensive Cancer CenterAllison Pledgie - Sidney Kimmel Comprehensive Cancer CenterLaurence J. Marton - NanGateTao Zhu - Sidney Kimmel Comprehensive Cancer CenterSaraswati Sukumar - Sidney Kimmel Comprehensive Cancer CenterBen Ho Park - Sidney Kimmel Comprehensive Cancer CenterBrian Blair - Sidney Kimmel Comprehensive Cancer CenterKeith Brenner - Sidney Kimmel Comprehensive Cancer CenterRobert A. Casero - Sidney Kimmel Comprehensive Cancer CenterNancy E. Davidson - Sidney Kimmel Comprehensive Cancer Center
- Resource Type
- Journal article
- Publication Details
- The Journal of biological chemistry, Vol.281(28), pp.19055-19063
- DOI
- 10.1074/jbc.M600910200
- PMID
- 16679312
- PMCID
- PMC3623667
- NLM abbreviation
- J Biol Chem
- ISSN
- 0021-9258
- eISSN
- 1083-351X
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 07/14/2006
- Academic Unit
- Internal Medicine
- Record Identifier
- 9984383911402771
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