PMID- 32455774
OWN - NLM
STAT- MEDLINE
DCOM- 20210225
LR  - 20210225
IS  - 2073-4409 (Electronic)
IS  - 2073-4409 (Linking)
VI  - 9
IP  - 5
DP  - 2020 May 21
TI  - HDAC3-ERalpha Selectively Regulates TNF-alpha-Induced Apoptotic Cell Death in MCF-7 Human 
      Breast Cancer Cells via the p53 Signaling Pathway.
LID - 10.3390/cells9051280 [doi]
LID - 1280
AB  - Tumor necrosis factor-alpha (TNF-alpha) plays a significant role in inflammation and 
      cancer-related apoptosis. We identified a TNF-alpha-mediated epigenetic mechanism of 
      apoptotic cell death regulation in estrogen receptor-alpha (ERalpha)-positive human 
      breast cancer cells. To assess the apoptotic effect of TNF-alpha, annexin V/ 
      propidium iodide (PI) double staining, cell viability assays, and Western 
      blotting were performed. To elucidate this mechanism, histone deacetylase (HDAC) 
      activity assay and immunoprecipitation (IP) were conducted; the mechanism was 
      subsequently confirmed through chromatin IP (ChIP) assays. Finally, we assessed 
      HDAC3-ERalpha-mediated apoptotic cell death after TNF-alpha treatment in ERalpha-positive 
      human breast cancer (MCF-7) cells via the transcriptional activation of p53 
      target genes using luciferase assay and quantitative reverse transcription PCR. 
      The TNF-alpha-induced selective apoptosis in MCF-7 cells was negatively regulated by 
      the HDAC3-ERalpha complex in a caspase-7-dependent manner. HDAC3 possessed a 
      p53-binding element, thus suppressing the transcriptional activity of its target 
      genes. In contrast, MCF-7 cell treatment with TNF-alpha led to dissociation of the 
      HDAC3-ERalpha complex and substitution of the occupancy on the promoter by the 
      p53-p300 complex, thus accelerating p53 target gene expression. In this process, 
      p53 stabilization was accompanied by its acetylation. This study showed that 
      p53-mediated apoptosis in ERalpha-positive human breast cancer cells was negatively 
      regulated by HDAC3-ERalpha in a caspase-7-dependent manner. Therefore, these proteins 
      have potential application in therapeutic strategies.
FAU - Park, Seung-Ho
AU  - Park SH
AD  - Department of Biomedical Sciences, Asan Medical Center, AMIST, University of 
      Ulsan College of Medicine, Seoul 05505, Korea.
AD  - Department of Pharmacology, University of Ulsan College of Medicine, Seoul 05505, 
      Korea.
FAU - Kim, Hyunhee
AU  - Kim H
AD  - Department of Biomedical Sciences, Asan Medical Center, AMIST, University of 
      Ulsan College of Medicine, Seoul 05505, Korea.
AD  - Department of Pharmacology, University of Ulsan College of Medicine, Seoul 05505, 
      Korea.
FAU - Kwak, Sungmin
AU  - Kwak S
AD  - Department of Biomedical Sciences, Asan Medical Center, AMIST, University of 
      Ulsan College of Medicine, Seoul 05505, Korea.
AD  - Department of Pharmacology, University of Ulsan College of Medicine, Seoul 05505, 
      Korea.
FAU - Jeong, Ji-Hoon
AU  - Jeong JH
AD  - Department of Biomedical Sciences, Asan Medical Center, AMIST, University of 
      Ulsan College of Medicine, Seoul 05505, Korea.
AD  - Department of Pharmacology, University of Ulsan College of Medicine, Seoul 05505, 
      Korea.
FAU - Lee, Jangho
AU  - Lee J
AD  - Korea Food Research Institute, Wanju-gun 55365, Korea.
FAU - Hwang, Jin-Taek
AU  - Hwang JT
AD  - Korea Food Research Institute, Wanju-gun 55365, Korea.
AD  - Department of Food Biotechnology, Korea University of Science & Technology, 
      Daejeon 34113, Korea.
FAU - Choi, Hyo-Kyoung
AU  - Choi HK
AD  - Korea Food Research Institute, Wanju-gun 55365, Korea.
FAU - Choi, Kyung-Chul
AU  - Choi KC
AD  - Department of Biomedical Sciences, Asan Medical Center, AMIST, University of 
      Ulsan College of Medicine, Seoul 05505, Korea.
AD  - Department of Pharmacology, University of Ulsan College of Medicine, Seoul 05505, 
      Korea.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200521
PL  - Switzerland
TA  - Cells
JT  - Cells
JID - 101600052
RN  - 0 (Estrogen Receptor alpha)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - EC 2.3.1.48 (E1A-Associated p300 Protein)
RN  - EC 2.3.1.48 (EP300 protein, human)
RN  - EC 3.4.22.- (Caspase 7)
RN  - EC 3.5.1.98 (Histone Deacetylases)
RN  - EC 3.5.1.98 (histone deacetylase 3)
SB  - IM
MH  - Acetylation
MH  - Apoptosis/*drug effects
MH  - Breast Neoplasms/*metabolism/*pathology
MH  - Caspase 7/metabolism
MH  - E1A-Associated p300 Protein/metabolism
MH  - Estrogen Receptor alpha/*metabolism
MH  - Female
MH  - Histone Deacetylases/*metabolism
MH  - Humans
MH  - MCF-7 Cells
MH  - Promoter Regions, Genetic
MH  - Protein Stability/drug effects
MH  - *Signal Transduction/drug effects
MH  - Tumor Necrosis Factor-alpha/*pharmacology
MH  - Tumor Suppressor Protein p53/*metabolism
PMC - PMC7290399
OTO - NOTNLM
OT  - ERalpha
OT  - HDAC3
OT  - TNF-alpha
OT  - apoptosis
OT  - p53
COIS- The authors declare no conflict of interest.
EDAT- 2020/05/28 06:00
MHDA- 2021/02/26 06:00
PMCR- 2020/05/01
CRDT- 2020/05/28 06:00
PHST- 2020/03/30 00:00 [received]
PHST- 2020/05/15 00:00 [revised]
PHST- 2020/05/19 00:00 [accepted]
PHST- 2020/05/28 06:00 [entrez]
PHST- 2020/05/28 06:00 [pubmed]
PHST- 2021/02/26 06:00 [medline]
PHST- 2020/05/01 00:00 [pmc-release]
AID - cells9051280 [pii]
AID - cells-09-01280 [pii]
AID - 10.3390/cells9051280 [doi]
PST - epublish
SO  - Cells. 2020 May 21;9(5):1280. doi: 10.3390/cells9051280.