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. 2000 Mar;46(3):359–366. doi: 10.1136/gut.46.3.359

Altered mRNA expression of glycosyltransferases in human colorectal carcinomas and liver metastases

T Petretti 1, W Kemmner 1, B Schulze 1, P Schlag 1
PMCID: PMC1727852  PMID: 10673297

Abstract

BACKGROUND/AIMS—Biosynthesis of carbohydrate structures is tissue specific and developmentally regulated by glycosyltransferases such as fucosyltransferases, sialyltransferases, and N-acetylgluco- saminyltransferases. During carcinogenesis, aberrant glycosylation leads to the development of tumour subpopulations with different adhesion properties. Therefore alterations in glycosyltransferase mRNA expression in colorectal carcinomas were examined by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR).
METHODS—Colorectal carcinoma specimens were classified and characterised according to the WHO/UICC system. Expression of fucosyltransferases FT-I, FT-III, FT-IV, FT-V, FT-VI, and FT-VII, sialyltransferases ST3Gal-I, ST3Gal-III, ST3Gal-IV, and ST6Gal-I, β1,4-galacto- syltransferase, and β1,6-Nacetylgluco- saminyltransferase V (GNT-V) was screened simultaneously in extracts of 22 homogenised tumour specimens by RT-PCR and compared with corresponding mucosa from each patient. Also 12 adenomas and 17 liver metastases of colorectal carcinomas were examined.
RESULTS—GNT-V expression was enhanced in colorectal adenomas (p = 0.039), carcinomas (p<0.001), and liver metastases of colorectal carcinomas (p<0.001). Also, expression of fucosyltransferase FT-IV was increased in colorectal adenomas (p = 0.039) and carcinomas (p<0.001). In addition, fucosyltransferase FT-I (p<0.001) and sialyltransferases ST6Gal-I (p = 0.004) and ST3Gal-III (p = 0.001) showed increased expression in carcinoma specimens. On the other hand, fucosyltransferase FT-III was less abundantly expressed in carcinomas exhibiting distant metastases (p = 0.046) and in highly invasive tumours (p = 0.041).
CONCLUSIONS—Glycosyltransferase mRNA expression is significantly altered in colorectal adenomas and carcinomas isolated from surgical specimens. RT-PCR determination of specific glycosyltransferases may be helpful for earlier detection of carcinomas and for tumour prognosis.


Keywords: colorectal carcinoma; adenomas; liver metastasis; glycosyltransferases; tumour prognosis; mRNA expression

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Figure 1  .

Figure 1  

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Glycosyltransferase expression in human colorectal tissue from case 3. Fluorescence of electrophoretically resolved, ethidium bromide stained polymerase chain reaction (PCR) products of β-actin and glycosyltransferase target sequences from colon mucosa, colon adenoma tissue, and colon carcinoma tissue is shown. Glycosyltransferases were amplified as described in Materials and methods. The upper band shows the reaction product of β-actin amplification. All amplicons were sequenced and compared with published sequences. First lane, molecular mass markers (bp). FT-I, H blood group α1,2-fucosyltransferase I; FTIII-VII, fucosyltransferases III-VII; STI-IV, sialyltransferases ST3Gal-I-IV; ST6, sialyltransferase ST6Gal-I; Gal-T, β1,4-galactosyltransferase; GNT, β1,6-N-acetylglucosaminyltransferase V. 

Figure 2  .

Figure 2  

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Glycosyltransferase expression in liver and liver metastases of a human colorectal carcinoma from case 35. Fluorescence of electrophoretically resolved, ethidium bromide stained polymerase chain reaction (PCR) products of β-actin and glycosyltransferase target sequences from normal liver tissue and liver metastases is shown. Glycosyltransferases were amplified as described in Materials and methods. The upper band shows the reaction product of β-actin amplification. All amplicons were sequenced and compared with published sequences. First lane, molecular mass markers (bp). FT-I, H blood group α1,2-fucosyltransferase I; FTIII-VII, fucosyltransferases III-VII; STI-IV, sialyltransferases ST3Gal-I-IV; ST6, sialyltransferase ST6Gal-I; Gal-T, β1,4-galactosyltransferase; GNT, β1,6-N-acetylglucosaminyltransferase V. 

Figure 3  .

Figure 3  

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Glycosyltransferase expression in human colorectal tissue. For semiquantitative analysis of the reverse transcription-polymerase chain reaction data, fluorescence of each sample was compared with that of β-actin co-amplified in the same tube. Standard deviations describe tumour heterogeneity not the accuracy of the assay system. FT-I, H blood group α1,2-fucosyltransferase I; FTIII-VI, fucosyltransferases III-VI; STI-IV, sialyltransferases ST3Gal-I-IV; ST6-I, sialyltransferase ST6Gal-I; GNT-V, β1,6-N-acetylglucosaminyltransferase V. 

Figure 4  .

Figure 4  

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Glycosyltransferase expression in liver metastases of human colorectal carcinomas. For semiquantitative analysis of the reverse transcription-polymerase chain reaction data, fluorescence of each sample was compared with that of β-actin co-amplified within the same tube. Standard deviations describe tumour heterogeneity not the accuracy of the assay system. FT-I, H blood group α1,2-fucosyltransferase I; FTIII-VI, fucosyltransferases III-VI; STI-IV, sialyltransferases ST3Gal-I-IV; ST6-I, sialyltransferase ST6Gal-I; GNT-V, β1,6-N-acetylglucosaminyltransferase V. 

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