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

Petretti, T; Kemmner, Wolfgang; Schulze, B; Schlag, Peter M.

doi:10.1136/gut.46.3.359

Cited by 124 publications

(85 citation statements)

References 48 publications

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“…In lung cancer the expression of FUT4 and FUT7 genes is related to poor prognosis (13). FUT4 was also observed to be significantly increased in gastric and colorectal carcinoma (14,15). FUT6 mRNA expression was detected specifically in pancreatic cancer tissues (16) and invasive as well as non-invasive bladder carcinoma cell lines (17), but not in normal pancreas or bladder.…”

Section: Introductionmentioning

confidence: 77%

Different expression levels of α3/4 fucosyltransferases and Lewis determinants in ovarian carcinoma tissues and cell lines

Escrevente

Machado²,

Brito³

et al. 2006

Int J Oncol

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Section: Introductionmentioning

confidence: 77%

Different expression levels of α3/4 fucosyltransferases and Lewis determinants in ovarian carcinoma tissues and cell lines

Escrevente

Machado²,

Brito³

et al. 2006

Int J Oncol

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“…adenocarcinomas and normal mucosa. [24][25][26] Although the down-regulation of expression of the Gal3ST-2 gene is evident as shown in Tables II, III, and Fig. 2, there exist substantial enzymatic activities in colonic non-mucinous adenocarcinoma.…”

Section: Discussionmentioning

confidence: 99%

Down‐regulation of Gal 3–O‐sulfotransferase‐2 (Gal3ST‐2) Expression in Human Colonic Non‐mucinous Adenocarcinoma

Seko¹,

Nagata²,

Yonezawa³

et al. 2002

Japanese Journal of Cancer Research

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Expression levels of sulfomucin in human colonic adenocarcinomas are lower than those in normal colonic mucosa; this should be in part caused by down-regulation of expression of sulfotransferases, but it remains unclear which Gal 3-O-sulfotransferase (Gal3ST) is responsible for the biosynthesis of sulfomucin. In this study, we first examined the substrate specificities of four Gal3STs cloned so far, and found that Galβ β β β1 → → → →3GlcNAcβ β β β1 → → → → 3Galβ β β β1 → → → →4Glc (LNT) can be utilized only byGal3ST-2 as an acceptor substrate. The substrate specificity of Gal3ST-2 is closely similar to those of Gal3ST activities present in human normal mucosa and adenocarcinomas, suggesting that Gal3ST-2 is the dominant Gal3ST in colon and colonic cancer. Secondly, using LNT as a substrate, we comparatively analyzed levels of Gal3ST-2 activities in non-mucinous adenocarcinoma, mucinous adenocarcinomas, and the adjacent normal mucosa. We found that levels of Gal3ST-2 activities in non-mucinous adenocarcinoma are significantly lower than those in the adjacent normal mucosa, while those in mucinous adenocarcinomas are not significantly different from those in the adjacent normal mucosa. Moreover, we showed by a competitive RT-PCR method that expression levels of transcript for Gal3ST-2 in non-mucinous adenocarcinoma are lower than those in normal mucosa. These results suggest that Gal3ST-2 is one of the enzymes responsible for biosynthesis of sulfomucin, and that expression levels of Gal3ST-2 are down-regulated in non-mucinous adenocarcinoma.Key words: Colon cancer -Sulfomucin -Sulfotransferase -Gal3ST -Type 1Sulfomucin is a glycoprotein containing large amounts of O-linked, sulfated glycans. It is well-known that expression levels of sulfomucin in colonic cancer are markedly lower than those in the adjacent normal mucosa. 1, 2)Yamori et al.3) explored a monoclonal antibody, 91.9H, recognizing sulfated glycans in sulfomucin, and Irimura et al. 4) and Matsushita et al. 5) showed that expression levels of the epitope in colonic adenocarcinomas are indeed lower than those in normal mucosa. Thereafter, Loveless et al. 6) showed that the minimum epitope moiety is the SO 3 − →3Galβ1→3(Fucα1→4)GlcNAcβ1→3Galβ1→ structure. These results suggest that the decrease of the epitope in colon cancer is at least partly associated with that of sulfomucin. We previously showed that levels of the enzymatic activities of β1,3-galactosyltransferase, which can synthesize the backbone structure of the 91.9H antigen, are lower in colonic adenocarcinomas than in the adjacent normal mucosa. 7) Thereafter, Salvini et al. 8) showed that expression of β3GalT-V gene is down-regulated in colonic adenocarcinomas, suggesting that β3GalT-V gene is involved in biosynthesis of the 91.9H antigen and its low expression in colonic adenocarcinomas. However, it remains unclear whether or not 3-O-sulfation at the Gal residue is also down-regulated in the course of colonic carcinogenesis. Gal3ST transfers sulfate from PAPS to the C-3 position of Gal residu...

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“…9) However, cells of epithelial origin usually contain a significant amount of transcripts for other fucosyltransferase isoenzymes that are capable of synthesizing sialyl Lewis a/x ; i.e., mainly fucosyltransferases III and VI. The mRNA level of these major fucosyltransferase isoenzymes in epithelial cells shows no significant difference between colon cancer tissues and non-malignant colonic epithelial cells, 32,33) nor does the level explain the increased synthesis of sialyl Lewis x in cancer. Fucosyltransferase VII makes a substantial contribution to the synthesis in cells such as leukemic cells, which do not contain fucosyltransferase III or VI.…”

Section: Induction Of Sialyl Lewis A/x Expression In Epithelial Cancementioning

confidence: 99%

“…The role of selectin-mediated cell adhesion in cancer metastasis has mostly been considered in relation to patients with colon cancers, where hematogenous metastasis to the liver is the main factor determining the prognosis. [32][33][34][35][36] The increased expression of genes for some glycosyltransferases has been detected in colon cancer cells. Besides glycosyltransferases, expression of the genes for some sugar transporters such as GLUT-1 or UDP-galactose transporter was shown to be increased in cancers and implicated in the enhanced expression of sialyl Lewis a/x .…”

Section: Induction Of Sialyl Lewis A/x Expression In Epithelial Cancementioning

confidence: 99%

Carbohydrate‐mediated cell adhesion in cancer metastasis and angiogenesis

et al. 2004

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

Abstract: 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.

Cited by 124 publications

References 48 publications

Different expression levels of α3/4 fucosyltransferases and Lewis determinants in ovarian carcinoma tissues and cell lines

Different expression levels of α3/4 fucosyltransferases and Lewis determinants in ovarian carcinoma tissues and cell lines

Down‐regulation of Gal 3–O‐sulfotransferase‐2 (Gal3ST‐2) Expression in Human Colonic Non‐mucinous Adenocarcinoma

Carbohydrate‐mediated cell adhesion in cancer metastasis and angiogenesis

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