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Jumbe SL, Porazinski SR, Oltean S, et al. The Evolutionarily Conserved Cassette Exon 7b Drives ERG's Oncogenic Properties. Transl Oncol. 2018;12(1):134-142doi: 10.1016/j.tranon.2018.09.001.
Jumbe, S. L., Porazinski, S. R., Oltean, S., Mansell, J. P., Vahabi, B., Wilson, I. D., & Ladomery, M. R. (2019). The Evolutionarily Conserved Cassette Exon 7b Drives ERG's Oncogenic Properties. Translational oncology, 12(1), 134-142. https://doi.org/10.1016/j.tranon.2018.09.001
Jumbe, Samantha L, et al. "The Evolutionarily Conserved Cassette Exon 7b Drives ERG's Oncogenic Properties." Translational oncology vol. 12,1 (2019): 134-142. doi: https://doi.org/10.1016/j.tranon.2018.09.001
Jumbe SL, Porazinski SR, Oltean S, Mansell JP, Vahabi B, Wilson ID, Ladomery MR. The Evolutionarily Conserved Cassette Exon 7b Drives ERG's Oncogenic Properties. Transl Oncol. 2019 Jan;12(1):134-142. doi: 10.1016/j.tranon.2018.09.001. Epub 2018 Oct 05. PMID: 30296658; PMCID: PMC6174920.
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Transl Oncol. 2019 Jan;12(1):134-142. doi: 10.1016/j.tranon.2018.09.001. Epub 2018 Oct 05.

The Evolutionarily Conserved Cassette Exon 7b Drives ERG's Oncogenic Properties.

Translational oncology

Samantha L Jumbe, Sean R Porazinski, Sebastian Oltean, Jason P Mansell, Bahareh Vahabi, Ian D Wilson, Michael R Ladomery

Affiliations

  1. Faculty of Health and Applied Sciences, University of the West of England, Coldharbour Lane, Frenchay, Bristol BS16 1QY, United Kingdom.
  2. Institute of Biomedical & Clinical Sciences, University of Exeter Medical School, St Luke's Campus, Heavitree Rd, Exeter, EX1 2LU, United Kingdom.
  3. Faculty of Health and Applied Sciences, University of the West of England, Coldharbour Lane, Frenchay, Bristol BS16 1QY, United Kingdom. Electronic address: [email protected].

PMID: 30296658 PMCID: PMC6174920 DOI: 10.1016/j.tranon.2018.09.001

Abstract

The oncogene ERG encodes an ETS family transcription factor and is implicated in blood, vascular, and bone development and in prostate, blood, and bone cancer. The ERG gene is alternatively spliced; of particular interest is its cassette exon 7b which adds 24 amino acids, in frame, to the transcriptional activation domain. Higher exon 7b inclusion rates are associated with increased cell proliferation and advanced prostate cancer. The 24 amino acids encoded by exon 7b show evolutionary conservation from humans to echinoderms, highlighting their functional importance. Throughout evolution, these 24 amino acids are encoded by a distinct short exon. Splice-switching oligonucleotides based on morpholino chemistry were designed to induce skipping of ERG exon 7b in MG63 osteosarcoma and VCaP prostate cancer cells. Induction of exon 7b skipping reduced cell proliferation and invasion, increased apoptosis in vitro, and reduced xenograft growth in vivo. We also show that ERG's exon 7b is required for the induction of tissue nonspecific alkaline phosphatase. Together, these findings show that the evolutionarily conserved cassette exon 7b is central to ERG's oncogenic properties.

Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.

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