Novel detection and differential utilization of a c-myc transcriptional block in colon cancer chemoprevention

Andrew J. Wilson, Anna Velcich, Diego Arango, Amy R. Kurland, Shailesh M. Shenoy, Rossanna C. Pezo, Jeffrey M. Levsky, Robert H. Singer, Leonard H. Augenlicht

Research output: Contribution to journalArticle

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Abstract

Mutations in the adenomatous polyposis coli (APC) gene, which initiate almost all human colon cancers, directly target the proto-oncogene, c-myc, by elevating β-catenin/T-cell factor (TCF) signaling. We have shown that agents ascribed chemopreventive activity for colon cancer in fact also stimulate β-catenin/TCF activity in vitro. Their effects on c-myc transcription were assayed using a novel variant of fluorescence in situ hybridization that detects c-myc transcription sites in intact nuclei. Increased transcriptional initiation of c-myc induced by the short-chain fatty acid, butyrate, consistent with elevated β-catenin/TCF activity, was efficiently abrogated by a block to transcriptional elongation, resulting in decreased c-myc expression. 1α,25-Dihydroxyvitamin D3 also induced transcriptional blockage. In contrast, the nonsteroidal anti-inflammatory drug, sulindac, increased c-myc expression, an effect attributable at least in part to its failure to induce transcriptional blockage. We have described a novel approach for evaluating the effects of chemopreventive agents on the expression of a gene critical in colonic tumorigenesis.

Original languageEnglish (US)
Pages (from-to)6006-6010
Number of pages5
JournalCancer Research
Volume62
Issue number21
StatePublished - Nov 1 2002

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TCF Transcription Factors
Catenins
Chemoprevention
Colonic Neoplasms
Sulindac
APC Genes
myc Genes
Volatile Fatty Acids
Butyrates
Calcitriol
Fluorescence In Situ Hybridization
Carcinogenesis
Anti-Inflammatory Agents
Gene Expression
Mutation
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Novel detection and differential utilization of a c-myc transcriptional block in colon cancer chemoprevention. / Wilson, Andrew J.; Velcich, Anna; Arango, Diego; Kurland, Amy R.; Shenoy, Shailesh M.; Pezo, Rossanna C.; Levsky, Jeffrey M.; Singer, Robert H.; Augenlicht, Leonard H.

In: Cancer Research, Vol. 62, No. 21, 01.11.2002, p. 6006-6010.

Research output: Contribution to journalArticle

Wilson AJ, Velcich A, Arango D, Kurland AR, Shenoy SM, Pezo RC et al. Novel detection and differential utilization of a c-myc transcriptional block in colon cancer chemoprevention. Cancer Research. 2002 Nov 1;62(21):6006-6010.
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