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Updated: Jul 11, 2026
16:24
Profiling of Estrogen-regulated MicroRNAs in Breast Cancer Cells
Published on: February 21, 2014
Trichostatin A and 5 Aza-2' deoxycytidine decrease estrogen receptor mRNA stability in ER positive MCF7 cells through
Peter Pryzbylkowski1, Oluwakemi Obajimi, Judith Clancy Keen
1Department of Medicine, Division of Molecular Medicine, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Rm 170 E&R Building, 401 Haddon Avenue, Camden, NJ 08103, USA.
Breast Cancer Research and Treatment
|September 25, 2007
Summary
Epigenetic drugs Trichostatin A (TSA) and 5-Aza 2'deoxycytidine (AZA) decrease estrogen receptor alpha (ER) in ER-positive breast cancer by reducing ER mRNA stability via HuR protein. This offers a novel anti-estrogenic mechanism.
Area of Science:
- Molecular Biology
- Epigenetics
- Cancer Research
Background:
- Estrogen receptor alpha (ER) is crucial in ER-positive breast cancer.
- Epigenetic modifications like histone deacetylation and DNA methylation regulate gene expression.
- Pharmacologic inhibitors Trichostatin A (TSA) and 5-Aza 2'deoxycytidine (AZA) target these epigenetic mechanisms.
Purpose of the Study:
- To investigate the differential effects of TSA and AZA on ER levels in ER-positive versus ER-negative breast cancer cells.
- To elucidate the molecular mechanisms underlying TSA/AZA-induced changes in ER expression.
- To identify potential novel anti-estrogenic strategies in ER-positive breast cancer.
Main Methods:
- Treatment of ER-positive (MCF7) and ER-negative breast cancer cell lines with TSA and AZA.
- Analysis of ER mRNA and protein levels.
- RNA stability assays using Actinomycin D.
- Investigation of protein interactions with the ER 3'UTR.
- RNA immunoprecipitation and siRNA-mediated knockdown of HuR.
Main Results:
- TSA/AZA treatment decreased ER mRNA and protein levels in ER-positive MCF7 cells, but increased them in ER-negative cells.
- The decrease in ER levels in MCF7 cells was dependent on interaction with the ER 3'UTR.
- TSA/AZA treatment reduced ER mRNA stability by altering the subcellular localization of the RNA-binding protein HuR.
- Knockdown of HuR mimicked the effect of TSA/AZA on ER mRNA stability.
Conclusions:
- Epigenetic modulators TSA and AZA exert anti-estrogenic effects in ER-positive breast cancer by decreasing ER mRNA stability.
- This mechanism involves the modulation of HuR subcellular distribution, impacting ER mRNA stability.
- Altering HuR localization represents a novel anti-estrogenic strategy for ER-positive human breast cancer.
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