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Author Noh, Hyunggyun ♦ Park, Joonwoo ♦ Shim, Myeongguk ♦ Lee, YoungJoo
Source United States Department of Energy Office of Scientific and Technical Information
Content type Text
Language English
Subject Keyword APPLIED LIFE SCIENCES ♦ ANOXIA ♦ CELL PROLIFERATION ♦ DEPTH ♦ ESTROGENS ♦ GENES ♦ HISTONES ♦ IN VITRO ♦ IN VIVO ♦ MAMMARY GLANDS ♦ NEOPLASMS ♦ RECEPTORS ♦ THERAPY
Abstract Estrogen receptor (ER) is a crucial determinant of resistance to endocrine therapy, which may change during the progression of breast cancer. We previously showed that hypoxia induces ESR1 gene repression and ERα protein degradation via proteasome-mediated pathway in breast cancer cells. HDAC plays important roles in the regulation of histone and non-histone protein post-translational modification. HDAC inhibitors can induce epigenetic changes and have therapeutic potential for targeting various cancers. Trichostatin A exerts potent antitumor activities against breast cancer cells in vitro and in vivo. In this report, we show that TSA augments ESR1 gene repression at the transcriptional level and downregulates ERα protein expression under hypoxic conditions through a proteasome-mediated pathway. TSA-induced estrogen response element-driven reporter activity in the absence of estrogen was synergistically enhanced under hypoxia; however, TSA inhibited cell proliferation under both normoxia and hypoxia. Our data show that the hypoxia-induced repression of ESR1 and degradation of ERα are enhanced by concomitant treatment with TSA. These findings expand our understanding of hormone responsiveness in the tumor microenvironment; however, additional in-depth studies are required to elucidate the detailed mechanisms of TSA-induced ERα regulation under hypoxia. - Highlights: • TSA augments ESR1 gene repression at the transcriptional level under hypoxia. • TSA downregulates ERα protein expression under hypoxia. • TSA-induced ERα regulation under hypoxia is essential for understanding the behavior and progression of breast cancer.
ISSN 0006291X
Educational Use Research
Learning Resource Type Article
Publisher Date 2016-02-12
Publisher Place United States
Journal Biochemical and Biophysical Research Communications
Volume Number 470
Issue Number 3


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