Butyrate and Vitamin D-3 Induce Transcriptional Attenuation at the Cyclin D1 Locus in Colonic Carcinoma Cells

Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10467, USA.
Journal of Cellular Physiology (Impact Factor: 3.84). 03/2009; 218(3):638-42. DOI: 10.1002/jcp.21642
Source: PubMed


In stimulating maturation of colonic carcinoma cells, the short chain fatty acid butyrate, and 1alpha,25-dihydroxyvitamin D(3), were shown to attenuate transcription of the cyclin D1 gene, giving rise to truncated transcripts of this locus. Moreover, a sequence which is highly conserved in the human, mouse, rat, and dog genome was found in the 4 kb long intron 3 of the human cyclin D1 gene, and is capable of forming a hairpin structure similar to that of microRNA precursors. The expression of this sequence is also decreased by the attenuation. Thus, the transcriptional attenuation at the cyclin D1 locus not only down-regulates the expression of this key gene in mucosal cell maturation and tumorigenesis, but may also abrogate the generation of a molecule that encompasses this conserved sequence in cyclin D1 intron 3.

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Available from: Stefan Roepcke, Jun 30, 2014
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    • "In various cell culture models, however, butyrate inhibits proliferation, a result that has been linked either to the downregulation of cyclin D1 (Maier et al., 2009) or to the downregulation of the cyclin-dependent kinases (CDK) that overrule the concurrent increases in Dtype cyclins (Mathew et al., 2010). As D-type cyclins and their target kinases are responsible for G (gap) 0 /G 1 to S (synthesis) phase progression, the downregulation of either could plausibly explain the antiproliferative effect of butyrate in vitro. "
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    • "In line with this finding, we report that c-fos, a gene under the control of AP-1, showed similar pattern of super-induction, while it was not observed for cyclin D1. Butyrate was shown to attenuate cyclin D1 [41], [45] and decrease the level of other genes linked to cell proliferation such as cdk1 as well as inducing differentiation-specific genes including transglutaminase type I [46]. Moreover, butyrate was shown to induce c-fos and c-jun in cancer cell lines [47]. "
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