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  • Original Paper
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The ubiquitous and tissue specific promoters of the human SRC gene are repressed by inhibitors of histone deacetylases

Oncogene volume 21, pages 6340–6347 (2002)Cite this article

Abstract

Histone deacetylase inhibitors have generated keen interest as potential chemopreventive and chemotherapeutic agents due to their ability to induce cell cycle arrest, differentiation, and apoptosis in a diverse group of cancer derived cell lines. Activation of the 60 kDa non-receptor tyrosine kinase, c-Src, has been a consistent finding in many tumors and tumor derived cell lines, and has been implicated in these same cellular processes. We have shown that the histone deacetylase inhibitors, sodium butyrate and Trichostatin A, repressed c-Src mRNA and protein expression in a dose-dependent manner in cell lines derived from cancers of the colon, breast and liver. Our group has previously identified two distinct promoters that are responsible for SRC transcription, separated by a distance of approximately 1 kb. Sodium butyrate and Trichostatin A strongly inhibited activity of each of these highly disparate SRC promoters, demonstrating histone deacetylase inhibitors directly repress SRC transcription. This repression did not require protein neosynthesis and was not associated with a decrease in binding of protein factors essential for either promoter's activity. Our finding that sodium butyrate and Trichostatin A inhibit both SRC promoters suggest this oncogene may be a major target of these agents, and may explain in part their anti-cancer activity.

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Acknowledgements

This study was supported by operating grants to K Bonham from the Canadian Institute of Health Research (CIHR) and the Saskatchewan Cancer Agency. S Dehm was supported by a Natural Sciences and Engineering Research Council of Canada (NSERC) Scholarship.

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Author notes

  1. Calley L Kostyniuk and Scott M Dehm: Both authors contributed equally to this study

Authors and Affiliations

  1. Health Research Division, Cancer Research Unit, Saskatchewan Cancer Agency, 20 Campus Drive, Saskatoon, S7N 4H4, SK, Canada

    Danielle Batten & Keith Bonham

  2. Department of Biochemistry, University of Saskatchewan, Saskatoon, S7N 5E5, SK, Canada

    Calley L Kostyniuk & Scott M Dehm

Authors
  1. Calley L Kostyniuk
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  2. Scott M Dehm
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  3. Danielle Batten
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  4. Keith Bonham
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Correspondence to Keith Bonham.

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Kostyniuk, C., Dehm, S., Batten, D. et al. The ubiquitous and tissue specific promoters of the human SRC gene are repressed by inhibitors of histone deacetylases. Oncogene 21, 6340–6347 (2002). https://doi.org/10.1038/sj.onc.1205787

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  • DOI: https://doi.org/10.1038/sj.onc.1205787

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