American Association for Cancer Research
Browse
- No file added yet -

FIGURE 1 from Targeting the Clear Cell Sarcoma Oncogenic Driver Fusion Gene EWSR1::ATF1 by HDAC Inhibition

Download (977.93 kB)
figure
posted on 2023-07-03, 14:20 authored by Hirokazu Mae, Hidetatsu Outani, Yoshinori Imura, Ryota Chijimatsu, Akitomo Inoue, Yuki Kotani, Naohiro Yasuda, Sho Nakai, Takaaki Nakai, Satoshi Takenaka, Seiji Okada

Vorinostat treatment inhibits CCS cell growth in vitro and in vivo. A, MP-CCS-SY, SU-CCS1, Hewga-CCS, KAS, and NHDF cells were incubated with 0–30 μmol/L vorinostat for 48 hours, and the viable number of cells were estimated via a WST-8 assay (n = 3). The calculated IC50 values are shown in Table 1. B, Four CCS cell lines were treated with 0.3 and 3 μmol/L vorinostat or vehicle for 48 hours, stained with PI, and analyzed for cell-cycle stage using flow cytometry. C, Four CCS cell lines were treated with 0.3 to 10 μmol/L vorinostat or vehicle for 24 hours, and the protein expression levels of the apoptosis markers cleaved caspase-3 was detected using Western blotting. D and E, SU-CCS1 and Hewga-CCS cells were engrafted in nude mice, which were treated with 50 mg/kg vorinostat or vehicle via intraperitoneal administration (5 mice/group). Volume (D) and weight (E) of SU-CCS1 and Hewga-CCS tumors during treatment are shown (n = 5). Data in A, D, and E are means ± SDs. *, P < 0.05; **, P < 0.01 (Student t test).

Funding

MEXT | Japan Society for the Promotion of Science (JSPS)

Osaka Medical Research Foundation for Intractable Diseases

History

ARTICLE ABSTRACT

This study reveals the epigenetic and transcriptional suppression mechanism of the fusion oncogene EWSR1::ATF1 in clear cell sarcoma by histone deacetylase inhibitor treatment as well as identifying SOX10 as a transcription factor that regulates EWSR1::ATF1 expression.