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Breast Cancer Research
Published in: Breast Cancer Research 2/2010

Open Access 01-04-2010 | Research article

Trichostatin A enhances acetylation as well as protein stability of ERα through induction of p300 protein

Authors: Sung-Hye Kim, Hyun-Jin Kang, Hyelin Na, Mi-Ock Lee

Published in: Breast Cancer Research | Issue 2/2010

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Abstract

Introduction

Trichostatin A (TSA) is a well-characterized histone deacetylase (HDAC) inhibitor. TSA modifies the balance between HDAC and histone acetyltransferase activities that is important in chromatin remodeling and gene expression. Although several previous studies have demonstrated the role of TSA in regulation of estrogen receptor alpha (ERα), the precise mechanism by which TSA affects ERα activity remains unclear.

Methods

Transient transfection was performed using the Welfect-EX™Plus procedure. The mRNA expression was determined using RT-PCR. Protein expression and interaction were determined by western blotting and immunoprecipitation. The transfection of siRNAs was performed using the Oligofectamine™ reagent procedure.

Results

TSA treatment increased acetylation of ERα in a dose-dependent manner. The TSA-induced acetylation of ERα was accompanied by an increased stability of ERα protein. Interestingly, TSA also increased the acetylation and the stability of p300 protein. Overexpression of p300 induced acetylation and stability of ERα by blocking ubiquitination. Knockdown of p300 by RNA interference decreased acetylation as well as the protein level of ERα, indicating that p300 mediated the TSA-induced stabilization of ERα.

Conclusions

We report that TSA enhanced acetylation as well as the stability of the ERα protein by modulating stability of p300. These results may provide the molecular basis for pharmacological functions of HDAC inhibitors in the treatment of human breast cancer.
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Metadata
Title
Trichostatin A enhances acetylation as well as protein stability of ERα through induction of p300 protein
Authors
Sung-Hye Kim
Hyun-Jin Kang
Hyelin Na
Mi-Ock Lee
Publication date
01-04-2010
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 2/2010
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr2562

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