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Mol Carcinog. 2016 Oct;55(10):1411-23. doi: 10.1002/mc.22384. Epub 2015 Aug 27.

The TFG-TEC oncoprotein induces transcriptional activation of the human β-enolase gene via chromatin modification of the promoter region.

Author information

1
Laboratory of Molecular and Cellular Biology, Department of Life Science, Sogang University, Seoul, Korea.
2
Laboratory of Molecular and Cellular Biology, Department of Life Science, Sogang University, Seoul, Korea. jkim@sogang.ac.kr.

Abstract

Recurrent chromosome translocations are the hallmark of many human cancers. A proportion of human extraskeletal myxoid chondrosarcomas (EMCs) are associated with the characteristic chromosomal translocation t(3;9)(q11-12;q22), which results in the formation of a chimeric protein in which the N-terminal domain of the TRK-fused gene (TFG) is fused to the translocated in extraskeletal chondrosarcoma (TEC; also called CHN, CSMF, MINOR, NOR1, and NR4A3) gene. The oncogenic effect of this translocation may be due to the higher transactivation ability of the TFG-TEC chimeric protein; however, downstream target genes of TFG-TEC have not yet been identified. The results presented here, demonstrate that TFG-TEC activates the human β-enolase promoter. EMSAs, ChIP assays, and luciferase reporter assays revealed that TFG-TEC upregulates β-enolase transcription by binding to two NGFI-B response element motifs located upstream of the putative transcription start site. In addition, northern blot, quantitative real-time PCR, and Western blot analyses showed that overexpression of TFG-TEC up-regulated β-enolase mRNA and protein expression in cultured cell lines. Finally, ChIP analyses revealed that TFG-TEC controls the activity of the endogenous β-enolase promoter by promoting histone H3 acetylation. Overall, the results presented here indicate that TFG-TEC triggers a regulatory gene hierarchy implicated in cancer cell metabolism. This finding may aid the development of new therapeutic strategies for the treatment of human EMCs.

KEYWORDS:

TFG-TEC; chromosomal translocation; fusion protein; human extraskeletal myxoid chondrosarcoma; human β-enolase gene; transcription activation

PMID:
26310886
DOI:
10.1002/mc.22384
[Indexed for MEDLINE]

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