The transition from normality to malignancy in colorectal cancer is characterized by alterations in the expression of genes associated with the maintenance of tissue homoeostasis. Butyrate, a product of microbial fermentation of dietary fibre in the colon, is known to regulate a number of genes associated with the processes of proliferation, differentiation and apoptosis of colonic epithelial cells, and, hence, homoeostasis of colonic tissue. We have shown previously that the transport of butyrate into colonocytes is of fundamental importance to butyrate's regulatory ability, and therefore sought to assess the expression profile of butyrate-responsive genes in colon cancer tissue, where the expression of the colonic luminal-membrane butyrate transporter, MCT1 (monocarboxylate transporter 1), is significantly down-regulated. In the present paper, we first employed microarray analysis to assess global changes in butyrate-responsive genes using HT29 human colon carcinoma cells treated with butyrate. There was consistency in the butyrate response of selected genes in two other human colonic cell lines (HCT116 and AA/C1) using quantitative real-time PCR. Furthermore, we report that expression levels of selected butyrate-responsive genes involved in the processes of proliferation, differentiation and apoptosis, are deregulated in colon cancer tissue, correlating with decreased expression of MCT1. These findings support our hypothesis that a reduction in MCT1 expression, and hence butyrate transport, can lead to a reduction in the intracellular butyrate levels required to regulate gene expression. Collectively, our results highlight the important contribution of butyrate transport to the maintenance of tissue homoeostasis and disease prevention.
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Conference Article|
August 01 2005
The importance of colonic butyrate transport to the regulation of genes associated with colonic tissue homoeostasis
K. Daly;
K. Daly
1Epithelial Function and Development Group, Department of Veterinary Preclinical Sciences, University of Liverpool, Liverpool L69 7ZJ, U.K.
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M.A. Cuff;
M.A. Cuff
1Epithelial Function and Development Group, Department of Veterinary Preclinical Sciences, University of Liverpool, Liverpool L69 7ZJ, U.K.
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F. Fung;
F. Fung
1Epithelial Function and Development Group, Department of Veterinary Preclinical Sciences, University of Liverpool, Liverpool L69 7ZJ, U.K.
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S.P. Shirazi-Beechey
S.P. Shirazi-Beechey
1
1Epithelial Function and Development Group, Department of Veterinary Preclinical Sciences, University of Liverpool, Liverpool L69 7ZJ, U.K.
1To whom correspondence should be addressed (email spsb@liv.ac.uk).
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Publisher: Portland Press Ltd
Received:
March 31 2005
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2005 The Biochemical Society
2005
Biochem Soc Trans (2005) 33 (4): 733–735.
Article history
Received:
March 31 2005
Citation
K. Daly, M.A. Cuff, F. Fung, S.P. Shirazi-Beechey; The importance of colonic butyrate transport to the regulation of genes associated with colonic tissue homoeostasis. Biochem Soc Trans 1 August 2005; 33 (4): 733–735. doi: https://doi.org/10.1042/BST0330733
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