Up-regulation of a set of glycosyltransferase genes in human colorectal cancer.
The carbohydrate structures of glycoconjugates of cancer cells change markedly in comparison with those of noncancerous cells. We aimed to determine which glycosyltransferases are up-regulated or down-regulated in human colon cancer tissues in order for the dramatic change in carbohydrate structures to occur. The transcript levels of 12 glycosyltransferase genes were measured by a competitive reverse-transcription-PCR method in noncancerous and cancerous colorectal tissues. Eight well- to moderately differentiated and three poorly differentiated carcinomas were examined in comparison with noncancerous colon epithelial tissues adjacent to the carcinoma tissues. Two of the twelve glycosyltransferase genes, Fuc-TIV and ST3Gal II, were significantly up-regulated in all cancerous tissues regardless of the histologic features. Four genes, ST3Gal I, ST6Gal I, beta1,4GalT, and Core2 GnT, showed a tendency toward up-regulation, and a ST3Gal III gene showed a tendency toward down-regulation. The other genes, Fuc-TIII, Fuc-TVI, and ST3Gal IV, which were most abundantly expressed in colorectal tissues, did not show significant up-regulation except in the poorly differentiated carcinomas. The Fuc-TVII gene was expressed at a very low level and was not up-regulated, and the Fuc-TV gene was not expressed at all in the colorectal tissues. Interestingly, all of the 12 glycosyltransferase genes examined, except the Fuc-TV, Fuc-TVI, Fuc-TVII, and ST3Gal III genes, were markedly up-regulated in all of the poorly differentiated carcinomas. We concluded that multiple glycosyltransferase genes are up-regulated, probably leading to extensive glycosylation of glycoconjugates in colorectal cancer cells. Lastly, sialyl Lewis antigens, ie, sialyl Lewis x and a antigens, which are terminal epitopes of sugar chains and well known as tumor-associated antigens, were quantified by Western blotting analysis. Based on the levels of transcripts of the 12 enzymes together with the amounts of sialyl Lewis antigens, we concluded that Fuc-TIII, Fuc-TVI, and ST3Gal IV are mainly responsible for synthesis of the sialyl Lewis antigens in colon tissues, but are not responsible for the augmented expression of the antigens in colorectal cancers. The amounts of sialyl Lewis x and a epitopes on mucins in colon cancer tissues can thus be determined through combinatorial up-regulation of the multiple glycosyltransferase genes.
Kudo
T
T
Division of Cell Biology, Institute of Life Science, Soka University, Hachioji, Japan.
Ikehara
Y
Y
Togayachi
A
A
Morozumi
K
K
Watanabe
M
M
Nakamura
M
M
Nishihara
S
S
Narimatsu
H
H
D000328:Adult; D000368:Aged; D018395:CA-19-9 Antigen / Q000032:analysis; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D017931:DNA Primers; D005260:Female; D005647:Fucosyltransferases / Q000096:biosynthesis; D005700:Galactosyltransferases / Q000096:biosynthesis; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D016695:Glycosyltransferases / Q000096:biosynthesis*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016366:Open Reading Frames; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length
D018395:CA-19-9 Antigen; D017931:DNA Primers; D016695:Glycosyltransferases; D005647:Fucosyltransferases; D005700:Galactosyltransferases