Molecular changes in the expression of human colonic nutrient transporters during the transition from normality to malignancy

被引:107
作者
Lambert, DW
Wood, IS
Ellis, A
Shirazi-Beechey, SP [1 ]
机构
[1] Univ Liverpool, Dept Vet Preclin Sci, Epithelial Funct & Dev Grp, Liverpool L69 7ZJ, Merseyside, England
[2] Univ Liverpool, Dept Med, Liverpool L68 3GA, Merseyside, England
基金
英国生物技术与生命科学研究理事会;
关键词
colon cancer; butyrate transport; glucose transport; gene expression;
D O I
10.1038/sj.bjc.6600264
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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, MCTI. In this paper, using immunohistochemistry and in situ hybridisation histochemistry, we have determined the profile of MCTI protein and mRNA expression along the crypt to surface axis of healthy human colonic tissue, There is a gradient of MCTI protein expression in the apical membrane of the cells along the crypt-surface axis rising to a peak in the surface epithelial cells. MCTI mRNA is expressed along the cryptsurface 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 MCTI protein during transition from normality to malignancy. This was reflected in a corresponding reduction in MCTI mRNA expression, as measured by Northern analysis. Carcinoma samples displaying reduced levels of MCTI were found to express the high affinity glucose transporter, GLUTI, 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 MCTI in association with GLUTI could potentially be used as determinants of the malignant state of colonic tissue. (C) 2002 Cancer Research UK.
引用
收藏
页码:1262 / 1269
页数:8
相关论文
共 48 条
[1]   p21WAF1 is required for butyrate-mediated growth inhibition of human colon cancer cells [J].
Archer, SY ;
Meng, SF ;
Shei, A ;
Hodin, RA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (12) :6791-6796
[2]   MAMMALIAN PASSIVE GLUCOSE TRANSPORTERS - MEMBERS OF AN UBIQUITOUS FAMILY OF ACTIVE AND PASSIVE TRANSPORT PROTEINS [J].
BALDWIN, SA .
BIOCHIMICA ET BIOPHYSICA ACTA, 1993, 1154 (01) :17-49
[3]  
BROWN RS, 1993, CANCER, V72, P2979, DOI 10.1002/1097-0142(19931115)72:10<2979::AID-CNCR2820721020>3.0.CO
[4]  
2-X
[5]  
BUGAUT M, 1993, ANNU REV NUTR, V13, P217, DOI 10.1146/annurev.nu.13.070193.001245
[6]  
BURKITT DP, 1971, CANCER, V28, P3, DOI 10.1002/1097-0142(197107)28:1<3::AID-CNCR2820280104>3.0.CO
[7]  
2-N
[8]  
CHANTRET I, 1994, J CELL SCI, V107, P213
[9]   COLONIC FERMENTATION OF DIETARY FIBER TO SHORT CHAIN FATTY-ACIDS IN PATIENTS WITH ADENOMATOUS POLYPS AND COLONIC-CANCER [J].
CLAUSEN, MR ;
BONNEN, H ;
MORTENSEN, PB .
GUT, 1991, 32 (08) :923-928
[10]   KINETICS OF 3-ORTHO-METHYL-D-GLUCOSE TRANSPORT IN ISOLATED RAT HEPATOCYTES [J].
CRAIK, JD ;
ELLIOTT, KRF .
BIOCHEMICAL JOURNAL, 1979, 182 (02) :503-508