Lambert, D.W. orcid.org/0000-0001-9003-3145, Wood, I.S., Ellis, A. et al. (1 more author) (2002) Molecular changes in the expression of human colonic nutrient transporters during the transition from normality to malignancy. British Journal of Cancer, 86 (8). pp. 1262-1269. ISSN 0007-0920
Abstract
Healthy colonocytes derive 60-70% of their energy supply from short-chain fatty acids, particularly butyrate. Butyrate has profound effects on differentiation, proliferation and apoptosis of colonic epithelial cells by regulating expression of various genes associated with these processes. We have previously shown that butyrate is transported across the luminal membrane of the colonic epithelium via a monocarboxylate transporter, MCT1. In this paper, using immunohistochemistry and in situ hybridisation histochemistry, we have determined the profile of MCT1 protein and mRNA expression along the crypt to surface axis of healthy human colonic tissue. There is a gradient of MCT1 protein expression in the apical membrane of the cells along the crypt-surface axis rising to a peak in the surface epithelial cells. MCT1 mRNA is expressed along the crypt-surface axis and is most abundant in cells lining the crypt. Analysis of healthy colonic tissues and carcinomas using immunohistochemistry and Western blotting revealed a significant decline in the expression of MCT1 protein during transition from normality to malignancy. This was reflected in a corresponding reduction in MCT1 mRNA expression, as measured by Northern analysis. Carcinoma samples displaying reduced levels of MCT1 were found to express the high affinity glucose transporter, GLUT1, suggesting that there is a switch from butyrate to glucose as an energy source in colonic epithelia during transition to malignancy. The expression levels of MCT1 in association with GLUT1 could potentially be used as determinants of the malignant state of colonic tissue.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2002 Cancer Research UK. From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/ |
Keywords: | Aged; Aged, 80 and over; Blotting, Western; Cell Transformation, Neoplastic; Colon; Colonic Neoplasms; Female; Gene Expression Regulation, Neoplastic; Glucose Transporter Type 1; Humans; Immunohistochemistry; In Situ Hybridization; Male; Middle Aged; Monocarboxylic Acid Transporters; Monosaccharide Transport Proteins; Muscle Proteins; Precancerous Conditions; Protein Isoforms; RNA, Messenger; Symporters |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Clinical Dentistry (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 09 Aug 2016 10:54 |
Last Modified: | 09 Aug 2016 10:54 |
Published Version: | http://dx.doi.org/10.1038/sj.bjc.6600264 |
Status: | Published |
Publisher: | Cancer Research UK |
Refereed: | Yes |
Identification Number: | 10.1038/sj.bjc.6600264 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:100263 |