Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.4.99.6 (sialyltransferase)
 1,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study gives an evaluation of carcinoembryonic antigen (CEA), macrophage electrophoretic mobility test (MEM), sialyltransferase, galactosyltransferase isoenzyme (SGT), ribonuclease and reverse transcriptase as diagnostic aids in malignant diseases. CEA and sialyltransferase are of certain value in the monitoring of cancer, as their values in the serum may rise before progression of disease or relapse. Both tests are not reliable parameters in the early diagnosis of malignancy. Our results with regard to the MEM test have not proved in any way useful in the diagnosis of cancer. Our preliminary results appear to indicate that, provided further simplification of the method can be achieved, SGT isoenzyme determination seems to be a better means of diagnosing cancer. In view of inherent-methodological difficulties reverse transcriptase has, at present, no clinical application in the diagnosis of cancer.
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PMID:[Developments in the serological diagnosis of malignant diseases]. 746 58

Three melanomas of C57BL/6 mice (BL6, JB/MS, and JB/RH) share several phenotypic properties. All these cells contain melanoma-specific ecotropic C-type retrovirus that encodes melanoma-associated antigen recognizable by MM2-9B6 mAb. They do not express H-2Kb molecules, and the alpha-galactosyl epitopes (Gal alpha 1-3Gal beta 1-4GlcNAc-R) they fail to react with soybean agglutinin (SBA), peanut agglutinin (PNA), and vicia villosa (VV) lectins. Previously, we found that failure of BL6 melanoma cells to express alpha-galactosyl epitopes is due to down-regulation of alpha 1,3 galactosyltransferase (alpha 1,3GT) gene expression. To evaluate the possible role of alpha-galactosyl cell membrane carbohydrates in regulation of metastatic properties, individual clones isolated from BL6, JB/MS, and JB/RH melanomas were transfected with alpha 1,3GT cDNA. This resulted in appearance of alpha-galactosyl epitopes, as well as of carbohydrates reacting with SBA, PNA, or VV lectins, but did not affect expression of H-2 class I molecules or melanoma-associated antigen. Appearance of SBA, PNA, and VV lectin binding carbohydrates in the alpha 1,3GT gene-transfected melanoma cells is a result of reduction of cell membrane sialylation and unmasking of these carbohydrates. Reduction in cell membrane sialylation in the alpha 1,3GT gene-transfected melanoma cells is probably due to the competition between alpha 1,3GT with alpha 2,3 sialyltransferase or alha 2,6 sialyltransferase for the common acceptor N-acetyllactosamine in the Golgi apparatus. As a result of this competition, cell membranes of alpha 1,3GT gene-transfected melanoma cells became galactosylated and less sialylated. In parallel with alteration of cell membrane carbohydrates, transfection of the alpha 1,3GT gene leads to the loss of metastatic properties of the transfected melanoma cells in the immunocompetent and immunosuppressed C57BL/6 mice. Thus, the use of specific glycosyltransferase cDNA transfection presents direct experimental confirmation of the importance of cell membrane carbohydrates in the regulation of metastatic properties of tumor cells.
Cancer Res 1995 Sep 15
PMID:Alterations of cell surface carbohydrates and inhibition of metastatic property of murine melanomas by alpha 1,3 galactosyltransferase gene transfection. 754 89

The product of the MUC1 gene, the polymorphic epithelial mucin (PEM) is aberrantly glycosylated in breast and other carcinomas, resulting in exposure of normally cryptic peptide epitopes. PEM expressed by breast cancer cells contains more sialylated O-glycans and has a lower GlcNAc content than that expressed by normal cells. The exposure of peptide epitopes is thus thought to be due to the sugar side chains being shorter on the tumour-associated mucin. To investigate possible mechanisms underlying the different pattern of glycosylation in breast cancer cells, we analysed the pathways involved in the biosynthesis of O-glycan chains of mucins in normal and cancerous mammary epithelial cells. An immortalized mammary epithelial cells line originating from normal human milk. MTSV1-7, and three human breast cancer cell lines, BT20, MCF-7 and T47D, were studied. Glycosyltransferase activities assembling, elongating and terminating O-glycan core-1 [Gal beta 1-3GalNAc alpha-R] and core-2 [GlcNac beta 1-6 (Gal beta 1-3) GalNAc alpha-R] were present in the normal mammary cell line. Many of the glycosyltransferase activities were also expressed at variable levels in breast cancer cells. However, a sialyltransferase activity (CMP-sialic acid Gal beta 1-3GalNAc alpha 3-sialyltransferase) was increased several fold in all three cancer cell lines. Moreover, mammary cancer cell lines BT20 and T47D have lost the ability to synthesize core-2, as shown by the lack of UDP-GlcNAc: Gal beta 1-3GalNAc (GlcNAc to GalNAc) beta 6-GlcNAc-transferase activity, which corresponded to the absence of the mRNA transcript. However, MCF-7 breast cancer cells expressed this enzyme. Thus, the mechanism for the exposure of peptide epitopes in BT20 and T47D cells is proposed to be the loss of core-2 branching leading to shorter, sialylated O-glycan chains. A different mechanism is proposed for MCF-7 breast cancer cells.
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PMID:Mechanisms underlying aberrant glycosylation of MUC1 mucin in breast cancer cells. 758 8

We estimated the levels of free sialic acid and sialylated oligosaccharides excreted in the urine of normal donors (n = 10) and patients with gastric cancer (n = 6) and colorectal cancer (n = 4). The total sialic acid level in cancer patients was similar to that in normal donors. However, the ratios of glycosidically bound sialic acids to free sialic acid were higher in some advanced cancer patients than in the normal donors. A major component of sialylated oligosaccharides was N-acetylneuraminyl alpha (2-->3) lactose. The elevation of the urinary ratio of this sialylated oligosaccharide to free sialic acid observed in some advanced cancer patients in this study may reflect the elevation of sialyltransferase activity in tumor tissues.
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PMID:Elevation of ratio of urinary N-acetylneuraminlactose to free sialic acid in some advanced cancer patients. 771 10

Human colon cancer is associated with antigenic and structural changes in mucin-type carbohydrate chains (O-glycans). To elucidate the control of the biosynthesis of these O-glycans is colon cancer, we have studied glycosyltransferase and sulphotransferase activities involved in the assembly of elongated O-glycan structures. We analysed homogenates prepared from cancer tissue, adjacent normal and distal normal tissue from 20 patients. Several transferase activities showed pronounced changes in cancer tissue. The changes correlate with previous findings of a loss of O-glycans in cancer mucins, but did not always correlate with levels of Tn, sialyl-Tn, T and Lex antigens in homogenates or with the differentiation status and Duke's stages of the cancer tissue or the patient's blood type, sex and age. UDP-GlcNAc: Gal NAc-R beta 3-N-acetylglucosaminyltransferase (where GlcNAc is N-acetyl-D-glucosamine and GalNAc is N-acetyl-D-galactosamine) synthesizing O-glycan core 3, GlcNAc beta 1-3GalNAc-, CMP-sialic acid: GalNAc-peptide alpha 6-sialyltransferase synthesizing the sialyl-Tn antigen and sulphotransferase activities towards O-glycan core 1, Gal beta 1-3GalNAc-, were found to be decreased in cancer. UDP-GlcNAc: Gal beta 1-3GalNAc beta 6-N-acetylglucosaminyltransferase was also decreased in cancer concomitant with a loss of the ability to synthesize the I antigen and core 4, GlcNAc beta 1-6(GlcNAc beta 1-3) GalNAc-, CMP-sialic acid: Gal beta 1-3GalNAc-R alpha 3-sialyltransferase and GDP-fucose: Gal beta-R alpha 2-fucosyltransferase, synthesizing the blood group H determinant, were found to be 4- and 3- to 8-fold increased, respectively, in cancer compared to normal tissue. The data suggest that the biosynthesis of antigens and mucin-bound O-glycan structures in colon cancer is subject to complex control mechanisms.
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PMID:Alterations of O-glycan biosynthesis in human colon cancer tissues. 773 50

1. n-Butyrate, a short chain fatty acid produced by colonic fermentation, induces differentiation in human neoplastic cell lines, and reduces expression in vitro of a sialyltransferase that glycosylates N-linked glycoproteins in hepatoblastoma cells. Gangliosides are amphipathic, sialylated glycosphingolipids that undergo profound changes in many transformed cells and may protect neoplastic cells from host immune surveillance. Colonic mucosal cells are exposed to luminal short-chain fatty acid concentrations of up to 80 mmol/l, and there is some evidence that short-chain fatty acids may alter ganglioside expression in colon cancer cells. 2. Because of the importance of gangliosides in cancer pathogenesis, we investigated the effects of n-butyrate on ganglioside expression of colonic (human and murine) and non-colonic cancer cells. 3. Three separate colon cancer cell lines (LS174T, T84 and MCA-38), when butyrate treated, demonstrated striking amplification of specific individual gangliosides. However, the total lipid-bound sialic acid content of gangliosides of butyrate-treated LS174T cells diminished. In contrast to earlier reports, n-butyrate did not mediate expression of all gangliosides and specifically did not mediate expression of GM3. This effect persisted even after removal of butyrate. 4. In contrast, exposure of extracolonic cells to butyrate, including cervical cancer (HeLa) and laryngeal cancer (HEp-2) cell lines in this study and hepatoblastoma cells (Hep G2) in our previous work, caused no detectable changes in ganglioside expression. 5. In conclusion, our results indicate a relative tissue specificity of butyrate-mediated alterations in ganglioside expression that is not universal but is limited to specific gangliosides.
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PMID:n-Butyrate mediation of ganglioside expression of human and murine cancer cells demonstrates relative cell specificity. 778 51

A human colonic adenoma cell line PC/AA derived from a familial polyposis coli patient was passaged in culture to form an intermediate premalignant clonogenic variant AA/C1 and, upon treatment with differentiating and carcinogenic agents, a cell line AA/C1/SB10 which is tumourigenic in nude mice. These three mucin-secreting cell lines have been used as a model to study the changes in O-glycan biosynthesis during the progression to cancer. Several glycosyltransferases involved in the synthesis, elongation and termination of the common O-glycan core structures were found to decrease in the progression sequence towards adenocarcinoma. Higher activity of a number of enzymes was seen in the intermediate cell line. O-glycan biosynthesis in the original PC/AA cell line was closest to the normal human colonic phenotype, since all four common mucin O-glycan cores and their extended structures could be synthesized; core 3 beta 3-GlcNAc-transferase and alpha 6-sialytransferase acting on GalNAc-mucin were still detectable and core 2 beta 6-GlcNAc-transferase activity was accompanied by core 4 and I beta 6-GlcNAc-transferase activities. During progression towards adenocarcinoma, the expression of alpha 6-sialyltransferase, core 3 beta 3-GlcNAc-transferase, core 4 and I beta 6-GlcNAc-transferases were turned off. Using monoclonal antibodies, Tn antigen, sialyl-Tn antigen, O-acetyl-sialomucin and sialyl-Lea determinants were not detected in secreted or cellular mucin isolated from any of the cell lines. The exposure of MUC1 epitopes was seen in the malignant line, whereas sialyl-Lex determinants were found only in the premalignant PC/AA line. Sulfotransferase activities using core 1 substrate, Gal beta 1-3GalNAc alpha-benzyl, were high in PC/AA cells and progressively decreased upon development to adenocarcinoma, and this decrease correlated with mucin sulfation. In summary, the synthesis of less abundant, sialylated, fucosylated and extended, unbranched core 1 structures should be facilitated in the malignant cells. This is the first report of glycosyltransferase changes in human premalignant cells developing to tumourigenic cells. The data demonstrate that these cell lines are an excellent model to study the changes and regulation of mucin oligosaccharide biosynthesis during progression to cancer.
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PMID:O-glycan biosynthesis in human colorectal adenoma cells during progression to cancer. 802 Apr 79

The activity of sialyltransferases with different linkage specificities, of a Gal beta 1-4GlcNAc:alpha 2,6-sialyltransferase and a Gal beta 1-4GlcNAc:alpha 2,3-sialyltransferase, was studied in human colorectal tumor tissue from surgical specimens, normal mucosa, liver and liver metastases, and serum of patients suffering from colorectal carcinomas. While alpha 2,3-specific activity was equally high in tumor and mucosa samples, the activity of the alpha 2,6-specific enzyme was increased in tumor tissue and particularly in metastasizing tumors. Also, compared to healthy individuals, serum of patients suffering from metastasizing tumors contained a significantly higher activity of the alpha 2,6-specific enzyme. These results demonstrate that specific sialyltransferase isoforms are expressed in metastasizing tumors and that determination of such isoforms may be a new means for tumor detection and monitoring.
Cancer Lett 1993 Dec 20
PMID:Enhanced activity of CMP-neuAc:Gal beta 1-4GlcNAc:alpha 2,6-sialyltransferase in metastasizing human colorectal tumor tissue and serum of tumor patients. 831 49

Ehrlich ascites tumor cells (EAT cells) are routinely grown in the peritoneal cavity of mice. These cells, EAT-wt, grow in suspension and exhibit a high level of alpha-2,3-O-linked sialyltransferase activity with benzyl-T-antigen (Gal beta 1,3Ga1NAc-alpha-O-CH2C6H5) as acceptor. These cells also contain a very low level of alpha-2,6-O-linked and alpha-2,6-N-linked sialyltransferase activity. A variant of these cells, EAT-c, has been selected to grow in cell culture, attached to the surface of culture flasks. EAT-c cells exhibit a selective increase of two- to fivefold in the activity of alpha-2,6-N-linked sialyltransferase activity, using asialo-alpha 1-acid glycoprotein as acceptor. Since a similar selective increase has been previously observed in metastatic human colorectal cancer tissues, the EAT-wt/EAT-c cell system may serve as a good experimental model for the investigation of sialyltransferases and their cell surface sialylated products in relation to cancer, metastasis, and cell-cell interaction.
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PMID:Cultured Ehrlich ascites tumor cells show increased N-linked alpha 2,6-sialyltransferase activity. 851 12

In human colon carcinoma, increased amounts of sialic acids have been found and correlated with tumor progression. Further, the degree of O-acetylation of sialic acid residues in normal mucosa is higher than in colon carcinoma. Thus, tumor-associated sialylated antigens may be constitutively expressed in O-acetylated form in normal mucosa unreactive with the respective monoclonal antibodies. We have earlier demonstrated a colon carcinoma-associated expression of alpha 2,6-linked sialic acid residues with the Sambucus nigra agglutinin (SNA). We report now that de-acetylation of normal and transitional colonic mucosa, in contrast to sialyl-Tn antigen, does not result in SNA binding. Further, the alpha 2,6-linked sialic acid recognized by SNA is distinct from that of sialyl-Tn antigen. This is confirmed by Northern blotting detecting transcripts for alpha 2,6 sialyltransferase of N-glycoproteins and measurement of activity for this sialyltransferase. Blot analysis by SNA of colon carcinoma cells revealed few reactive glycoproteins. Quantitative differences in lectin labeling and sialyltransferase activity were found in HCT116 colon carcinoma cell sub-lines. Our data suggest that SNA binding in human colon carcinoma is due to de novo expression of a specific sialic acid present on selected glycoproteins.
Int J Cancer 1997 Mar 04
PMID:Colon carcinoma glycoproteins carrying alpha 2,6-linked sialic acid reactive with Sambucus nigra agglutinin are not constitutively expressed in normal human colon mucosa and are distinct from sialyl-Tn antigen. 905 58


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