계명대학교 의학도서관 Repository

Estrogen-related receptor γ is upregulated in liver cancer and its inhibition suppresses liver cancer cell proliferation via induction of p21 and p27

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Author(s)
Ji-Hyun KimYeon-Kyung ChoiJun-Kyu ByunMi-Kyung KimYu Na KangSeong Heon KimSungwoo LeeByoung Kuk JangKeun-Gyu Park
Keimyung Author(s)
Kang, Yu NaKim, Mi KyungJang, Byoung Kuk
Department
Dept. of Pathology (병리학)
Dept. of Internal Medicine (내과학)
Journal Title
Experimental and Molecular Medicine.
Issued Date
2016
Volume
48
Abstract
Orphan nuclear receptor estrogen-related receptor γ (ERRγ) regulates cell growth and tumorigenesis in various cancers. However,
the clinical relevance of ERRγ to hepatocellular carcinoma (HCC) remains unclear. Here we examined the clinical significance
of ERRγ in HCC and its potential as a therapeutic target. ERRγ levels in tissues from completely resected specimens from 190
HCC patients were examined immunohistochemically and their association with clinical stage and pathological grade was analyzed.
Small interfering RNA (siRNA)-mediated knockdown of ERRγ (siRNA-ERRγ) or an ERRγ inverse agonist, GSK5182, were also
used to examine the effects of ERRγ inhibition on the proliferation and growth of a human hepatoma cell line, PLC/PRF/5.
Immunohistochemical analysis revealed that tumor tissues showed higher levels of ERRγ-positivity than adjacent non-tumor lesions.
Tumors showing high levels of ERRγ immunoreactivity also had advanced tumor node metastasis (TNM) and Barcelona Clinic Liver
Cancer stages and a higher Edmondson–Steiner grade. In addition, high-level expression of ERRγ in tumors of advanced TNM
stage correlated with poorer overall survival. Treatment of PLC/PRF/5 cells with siRNA-ERRγ or GSK5182 inhibited proliferation
through G1 arrest, increased expression of p21 and p27 and decreased expression of phosphorylated retinoblastoma protein.
GSK5182-induced reactive oxygen species also suppressed the proliferation of PLC/PRF/5 cells. The present study showed that
ERRγ expression is clinically significant in HCC; therefore, it can be considered a biomarker for HCC diagnosis. Moreover, the
results provide a rationale for the use of ERRγ inhibitors such as GSK5182 as potential therapeutic agents.
Keimyung Author(s)(Kor)
강유나
김미경
장병국
Publisher
School of Medicine
Citation
Ji-Hyun Kim et al. (2016). Estrogen-related receptor γ is upregulated in liver cancer and its inhibition suppresses liver cancer cell proliferation via induction of p21 and p27. Experimental and Molecular Medicine., 48, e213–e213. doi: 10.1038/emm.2015.115
Type
Article
ISSN
1226-3613
DOI
10.1038/emm.2015.115
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/33197
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Internal Medicine (내과학)
1. School of Medicine (의과대학) > Dept. of Pathology (병리학)
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