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Altered mRNA expression of glycosyltransferases in human colorectal carcinomas and liver metastases
  1. T Petretti,
  2. W Kemmner,
  3. B Schulze,
  4. P M Schlag
  1. Robert-Rössle-Klinik at the Max Delbrück Centre for Molecular Medicine, Department of Surgery and Surgical Oncology, Charité, Campus Buch, 13125 Berlin, Germany
  1. Dr W Kemmner, Max Delbrück Centre for Molecular Medicine, Robert-Rössle-Str 10, D-13092 Berlin, Germanywkemmner{at}mde-berlin.de

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.

  • colorectal carcinoma
  • adenomas
  • liver metastasis
  • glycosyltransferases
  • tumour prognosis
  • mRNA expression

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Footnotes

  • Abbreviations used in this paper:
    RT-PCR
    reverse transcription-polymerase chain reaction
    PHA-L
    Phaseolus vulgarisleucoagglutinating lectin