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SHR Neuro Krebs Kardio Lipid Stoffw Microb

Mayr, C; Helm, K; Jakab, M; Ritter, M; Shrestha, R; Makaju, R; Wagner, A; Pichler, M; Beyreis, M; Staettner, S; Jaeger, T; Klieser, E; Kiesslich, T; Neureiter, D.
The histone methyltransferase G9a: a new therapeutic target in biliary tract cancer.
Hum Pathol. 2018; 72:117-126 Doi: 10.1016/j.humpath.2017.11.003
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Pichler Martin

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The histone methyltransferase G9a (EHMT2) is a key enzyme for dimethylation of lysine 9 at histone 3 (H3K9me2), a suppressive epigenetic mark. G9a is over-expressed in tumor cells and contributes to cancer aggressiveness. Biliary tract cancer (BTC) is a rare cancer with dismal prognosis due to a lack of effective therapies. Currently, there are no data on the role of G9a in BTC carcinogenesis. We analyzed G9a expression in n=68 BTC patient specimens and correlated the data with clinicopathological and survival data. Moreover, we measured G9a expression in a panel of BTC cell lines and evaluated the cytotoxic effect of G9a inhibition in BTC cells using established small-molecule G9a inhibitors. G9a was considerably expressed in about half of BTC cases and was significantly associated with grading and tumor size. Additionally, we observed significant differences of G9a expression between growth type and tumor localization groups. G9a expression diametrically correlated with Vimentin (positive) and E-Cadherin (negative) expression. Importantly, survival analysis revealed G9a as a significant prognostic factor of poor survival in patients with BTC. In BTC cells, G9a and H3K9me2 were detectable in a cell line-dependent manner on mRNA and/or protein level, respectively. Treatment of BTC cells with established small-molecule G9a inhibitors resulted in reduction of cell viability as well as reduced G9a and H3K9me2 protein levels. The present study strongly suggests that G9a contributes to BTC carcinogenesis and may represent a potential prognostic factor as well as a therapeutic target. Copyright © 2017 Elsevier Inc. All rights reserved.

Find related publications in this database (Keywords)
Biliary tract cancer
Histone methyltransferase
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