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

Calley L. Kostyniuk, Scott M. Dehm, Danielle Batten, Keith Bonham

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

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 nonreceptor 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.

Original languageEnglish (US)
Pages (from-to)6340-6347
Number of pages8
JournalOncogene
Volume21
Issue number41
DOIs
StatePublished - 2002
Externally publishedYes

Bibliographical note

Funding Information:
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.

Keywords

  • Butyrate
  • Histone deacetylase
  • Src
  • Transcription
  • Trichostatin A

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