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The histone deacetylase inhibitor trichostatin A sensitizes estrogen receptor alpha-negative breast cancer cells to tamoxifen

Cited 123 time in Web of Science Cited 132 time in Scopus
Authors
Jang, Eun Ryoung; Lim, Soo-Jeong; Lee, Eun Sook; Jeong, Gajin; Kim, Tae-You; Bang, Yung-Jue; Lee, Jong-Soo
Issue Date
2004-03
Citation
Oncogene, Vol.23 No.9, pp.1724-1736
Keywords
estrogen receptor alpha, betatamoxifen responsivenessHDAC inhibitorER alpha-negative breast cancer
Abstract
Many cases of breast cancer show loss of estrogen receptor (ER) alpha expression, which leads to unresponsiveness to antihormonal treatment even though there is no loss of the structurally and biochemically similar ER beta. ER activity is positively and negatively regulated by transcriptional regulators such as histone deacetylase (HDAC), which is known to be a negative ER regulator. Here, we evaluated using ER beta as an alternative target for tamoxifen therapy by treating ER alpha-negative, beta-positive breast cancer cells with the HDAC inhibitor trichostatin A (TSA), and testing whether tamoxifen responsiveness increased following upregulation of ER beta. TSA enhanced the overall ER transcriptional activity in these cells, as visualized by estrogen response element-regulated reporter and the expression of progesterone receptor, a known ER target, without ER alpha restoration. Additionally, TSA induced the expression and nuclear translocation of ER beta but not alpha, suggesting that these actions leading to increase of ER transcriptional activity are mediated through ER beta rather than alpha. Furthermore, following treatment with TSA, the formerly unresponsive MDA-MB-231 and Hs578T breast cancer cells became responsive to tamoxifen. However, reduction of ER beta expression by short interfering RNA abrogated this TSA-induced sensitization effect in these cells. Together, these results show that the HDAC inhibitor TSA sensitized ER alpha-negative, antihormone-unresponsive breast cancer cells to tamoxifen treatment possibly by upregulating ER beta activity.
ISSN
0950-9232
URI
https://hdl.handle.net/10371/173197
DOI
https://doi.org/10.1038/sj.onc.1207315
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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