Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.4.99.7 (sialyltransferase)
 1,534 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sialyltransferase activity (EC 2.4.99.6) was measured in the microsomal fraction of colorectal cancer cell lines using an assay based on the incorporation of [14C]CMP-sialic acid into asialofetuin. In the poorly differentiated lines MIP101 and Clone A, sialyltransferase activity had a Vmax of 0.36 and 0.31 nmol/mg protein/h, respectively, while the moderately differentiated to well-differentiated cell lines HT-29, CCL188, and CX-1 had Vmaxs of 2.46, 1.05, and 1.24 nmol/mg protein/h, respectively. All cell lines tested had a Km of 15.4 (+/- 0.7)(SD) mumol/liter. The better differentiated cells had higher levels of sialyltransferase activity, which correlated with their higher levels of sialic acid and their enhanced ability to form liver metastases in the nude mouse following intrasplenic injection compared to the poorly differentiated cell lines. Treatment of the cell lines with KI-8110, a CMP-sialic acid derivative which prevents incorporation of sialic acid into glycoconjugates, resulted in reduced formation of hepatic metastases by the colorectal carcinoma cell lines in the nude mouse model. It is suggested that reduced sialylation of adhesion molecules such as carcinoembryonic antigen may change the biology of the tumor cell, one consequence of which is the prevention of implantation of the cells into distant sites, resulting in a reduced incidence of metastases.
Cancer Res 1992 Apr 01
PMID:Sialyltransferase activity and hepatic tumor growth in a nude mouse model of colorectal cancer metastases. 131 99

Many previous studies have implicated cell surface saccharides, and sialylglycoconjugates in particular, as important mediators of tumor cell metastasis. In this report, we have used three different specific sialidases and a highly sensitive high-performance liquid chromatographic sialic acid assay to probe the cell surfaces of several murine adrenal carcinoma variants. In contrast to several earlier studies on other metastatic variants, we find no significant differences in the overall levels of cell surface or total cellular sialic acid among three Y1 murine adrenal carcinoma variants with widely different metastatic phenotypes. However, using highly purified, linkage-specific sialyltransferases, in conjunction with V. cholerae sialidase, to probe the cell surface saccharide topography of specific penultimate oligosaccharides, we do find striking differences in oligosaccharide structures underlying the sialic acid moieties. Two tumorigenic and metastatic variants (F2 and F4) contain about 6-fold more penultimate Gal beta 1----4GlcNAc sialylation sites than a related tumorigenic but nonmetastatic variant (HSR) when CMP-[3H]-N-acetylneuraminic acid and the Gal beta 1----4GlcNAc alpha 2,6 sialyltransferase are used to probe the adrenal carcinoma cell surfaces. The metastatic variants also are found to contain 4- to 4.5-fold more Gal beta 1----3GalNAc sialylation sites than the nonmetastatic variant when the Gal beta 1----3GalNAc alpha 2,3 sialyltransferase is used as a cell surface probe. Earlier work, which used the same sialyltransferase probes on sialidase-treated murine melanoma variants (A. Passaniti and G. W. Hart, J. Biol. Chem., 263: 7591-7603, 1988), also showed similar quantitative differences in penultimate structures between metastatic variants. However, in contrast to the adrenal carcinoma cells, the highly metastatic melanoma cells have severalfold lower levels of sialylatable penultimate Gal beta 1----4GlcNAc and Gal beta 1----3GalNAc saccharides compared to their nonmetastatic counterparts. Thus, while the precise structural alterations or surface accessibilities of penultimate saccharides appear to be cell type dependent, these results suggest that pronounced changes in penultimate cell surface sialo-oligosaccharide moieties occur during progression to a malignant phenotype in two widely different tumor systems. These types of alterations in the underlying penultimate oligosaccharide structures of cell surface sialoglycoconjugates may be a common feature of highly metastatic cells arising from very different tumor cell types.
Cancer Res 1992 Apr 15
PMID:Adrenal carcinoma tumor progression and penultimate cell surface oligosaccharides. 155 26

The gangliosides of human hepatoma biopsies, human hepatoma cell lines, and diethylnitrosamine-induced rat hepatomas were examined. These malignant tissues all expressed increased content of disialolactosylceramide (GD3) with respect to their normal counterparts. During the induction of rat hepatoma by diethylnitrosamine, an increase in GD3 levels appeared as early as 12 wk after initiation of diethylnitrosamine, concurrent with the appearance of precancerous hepatocytes. GD3 levels gradually increased to a peak of 4 times that of normal rat liver at 20 wk. CMP-NeuAc:GM3 sialyltransferase, the enzyme that synthesizes GD3 by transfer of sialic acid to GM3, also had tumor-associated elevation during the course of diethylnitrosamine-induction of rat hepatomas. To investigate the relationship of oncogene transformation and changes in ganglioside biosynthesis, NIH 3T3 cells transfected DNAs from human hepatoma or nasopharyngeal carcinoma were studied. The transfectants each expressed the same ganglioside composition, including a detectable level of GD3, as well as enhanced activity of CMP-NeuAc:GM3 sialyltransferase. A correlation between the tumor DNA transfection and the augmentation of GD3 in malignant cells is discussed. Because of the early appearance of GD3 in hepatoma and its possible relationship to oncogene activation, GD3 may be a potentially useful early tumor marker.
Cancer Res 1990 Dec 01
PMID:Enhanced expression of ganglioside GD3 in human and rat hepatocellular carcinoma cells and NIH 3T3 cells transfected with human tumor DNAs. 170 52

The activity of an alpha 2,6 sialyltransferase acting on N-acetyllactosaminic sequences (alpha 2,6 ST E.C. 2.4.99.1) has previously been found to be increased in 90% of human colon cancer specimens. In the present study, the alpha 2,6 ST activity of 6 human colon cancer cell lines grown in culture was compared with that expressed by the corresponding nude mice xenografts and by the cell lines derived from the xenografts. We found that xenografts of COLO 205, HT-29, SW 620, SW 948 and SW 948 FL (a non-adherent sub-line of SW 948) cells express an alpha 2,6 ST activity much higher than that of the in vitro-grown cells. SW 48 cells grown either in culture or as xenografts lack the enzyme activity. All the xenograft-derived cell lines except HT-29 retained the increased alpha 2,6 ST activity at least for the first 6 passages. Those derived from SW 948 xenografts showed an enrichment of round, non-adherent cells, strongly reactive with the NeuAc alpha 2,6 Gal/GalNAc-specific lectin from Sambucus nigra (SNA), thus indicating that a selection of these cells has occurred.
Int J Cancer 1992 Jan 21
PMID:Enhanced CMP-NeuAc:Gal beta 1,4GlcNAc-R alpha 2,6 sialyltransferase activity of human colon cancer xenografts in athymic nude mice and of xenograft-derived cell lines. 173 May 28

In a previous work we found that human colorectal cancer tissues express increased levels of an alpha 2,6 sialyltransferase (alpha 2,6 ST) acting on N-acetyllactosaminic sequences (E.C. 2.4.99.1). In this study we have taken advantage of the known specificity of elderberry bark lectin (Sambucus nigra agglutinin, SNA) for NeuAc alpha 2, 6Gal/GalNAc structures to investigate the relationship between expression of alpha 2,6 sialyltransferase activity and occurrence of alpha 2,6-sialylated oligosaccharide sequences in human colorectal cancer cell lines. Three cell lines with opposite adhesion properties were used in this study: SW 948 cells grow adherent to the culture flask surface and express very low levels of enzyme activity; COLO 205 cells grow in non-adherent form and express the highest levels of alpha 2,6 ST activity; A non-adherent subline of SW 948 cells (SW 948 FL) was isolated and found to express high levels of alpha 2,6 ST activity. By using SNA-Sepharose chromatography we found that expression of alpha 2,6 ST activity correlates with the extent of alpha 2,6-sialylation of N-linked chains of glycoproteins but not with the presence of alpha 2,6-sialylated glycolipids.
Int J Cancer 1991 Jan 21
PMID:Alpha 2,6 sialylation of N-acetyllactosaminic sequences in human colorectal cancer cell lines. Relationship with non-adherent growth. 189 84

In forty-one carcinomas and sixteen benign lesions (fibroadenoma and mastopathy) of the human breast, immunohistochemical expression of sialylated and non-sialylated forms of both Lea and Lex, and the A, B, and H type 2 blood group substances were studied by using an indirect immunoperoxidase staining. In normal ductal epithelium and benign lesion of breast, Lewis-related antigens were mostly expressed. Breast carcinomas showed these antigens with the following frequencies: Lea, 31.7% (13/41); sialyl Lea, 56.1% (23/41); Lex, 46.3% (19/41); sialyl Lex, 68.3% (28/41); A/B/H type 2, 38.1% (16/41). Sialylated forms of Lea and Lex were observed more frequently than their respective non-sialylated forms in breast carcinomas. In both one normal epithelium and four carcinomas of breast with Le(a-b-) phenotype, the expressions of type 2 antigens were observed, while type 1 antigens were not consistently expressed. Although compatible expression was observed in all specimens of both normal epithelium and benign lesion of breast, twenty-four cases with the deletion of A and/or B antigens, six cases with H type 2 accumulation and one case with incompatible expression were demonstrated in breast carcinoma. Thirty-one breast carcinomas which showed the deletion of A/B/H type 2 expressed the Lewis-related antigens more frequently than nine cases which showed compatible expression. These results suggested that the activation of terminal fucosyltransferase and sialyltransferase as well as inactivation of some glycosyltransferases had occurred in cancer cell membrane, and sialyl Lex, defined by a new monoclonal antibody CSLEX1, may be useful as a tumor-associated antigen independent of Lewis blood group type in breast cancer.
Jpn J Cancer Res 1991 May
PMID:Immunohistochemical expression of blood group substances and related carbohydrate antigens in breast carcinoma. 190 2

Partial or total loss of chromosome 22 is often associated with tumors of the central nervous system and in particular with meningiomas. As in the case of other tumors, the ganglioside pattern is modified in transformed tissues. Cytogenetic analysis of 30 human meningiomas has been performed and the results compared to biochemical analysis of ganglioside distribution on the membrane surface. The meningiomas were divided into 2 groups on the basis of the presence or absence of chromosome 22. Thirteen tumors exhibited partial or total monosomy of the chromosome, whereas 17 were normal or showed other chromosomal anomalies. The GM3 and GD3 content of the meningiomas belonging to the 2 groups revealed a significant correlation between amount and reciprocal ratio of these 2 gangliosides and cytogenetic data. Tumors with monosomy 22 had a higher content of ganglioside GD3 than samples without monosomy 22, where the main ganglioside was GM3. Other gangliosides such as GM1, GD1a, GD1b and GT were present in various amounts in the 2 groups. Considering the biosynthetic pathway of gangliosides, we hypothesize the involvement of a gene located on chromosome 22 in the regulation of the enzymes which catalyze either GD3 synthesis (sialyltransferase 2, SAT-2) or its degradation to GM3 (neuraminidase).
Int J Cancer 1991 Feb 01
PMID:Correlation between cytogenetic data and ganglioside pattern in human meningiomas. 199 40

The role of acidic glycosphingolipids in cell growth and differentiation was investigated using the multipotent leukemia cell line K562. When GM3 was added to cell culture media, the growth of K562 cells was remarkably inhibited and the cells were shown to have megakaryocytoid morphology. Ultrastructural study demonstrated that K562 cells treated with GM3 had platelet peroxidase-positive structures, which were considered to be the specific marker of megakaryocyte. Furthermore, AP-3 directed against an epitope present on membrane glycoprotein IIIa reacted with the GM3-treated cells. Free N-acetylneuraminic acid, GM1, GM2, GD1a, and a mixture of bovine brain gangliosides containing GD1a and GT1b did not affect growth of K562 cells or show morphological changes. According to chemical analyses, GM3 content increased in megakaryocytoid differentiation induced by tetradecanoylphorbol-13-acetate, whereas GM3 decreased in erythroid differentiation induced by hemin. Enzymatic analysis showed that the GM3 increase during megakaryocytoid differentiation was a result of the sialyltransferase activation. These results indicated that exogenous GM3 induced differentiation of K562 cells into a "GM3-rich" lineage, i.e., mainly megakaryocytoid lineage, and that GM3 accumulation in the GM3-rich lineage was the result of the activation of GM3 synthase. These findings strongly suggested that GM3 ganglioside, a minor membrane component, has a crucial role in not only the differentiation induction but also the determination of the differentiation direction in pluripotent K562 cells.
Cancer Res 1991 Apr 01
PMID:Ganglioside GM3 can induce megakaryocytoid differentiation of human leukemia cell line K562 cells. 200 80

CMP-N-acetylneuraminic acid: glycoprotein sialyltransferase activities were assayed in microsomal fractions from chicken liver and hepatoma, induced by the leukosis virus strain Mc-29, using asialofetuin as the substrate acceptor of N-acetylneuraminic acid. The effect of some nucleotides and metal ions on the enzyme activity was investigated. Kinetic studies revealed that the Km values toward asialofetuin at a saturation concentrations of CMP-N-acetylneuraminic acid for both liver and hepatoma enzymes are very closed, while V value was lower for the tumor enzyme. The liver and hepatoma enzymes have no exogenous Mn cations requirement and are inhibited by CTP, CMP and ATP. CMP was shown to act as a competitive inhibitor with an apparent Ki of 0.24 mM for the liver and 0.16 mM for hepatoma enzyme, respectively.
Cancer Biochem Biophys 1990 Nov
PMID:Partial characterization of microsomal sialyltransferase from chicken liver and hepatoma Mc-29: I. Effect of nucleotides and metal ions. 208 38

Microsomal sialyltransferase was assayed in chicken liver and hepatoma Mc-29 utilizing liver and hepatoma microsomal glycoprotein fractions, treated with Triton X-100, as exogenous acceptors. In a homologous assay system containing enzyme and acceptor from one and the same tissue no quantitative dependence of enzyme activity was revealed with increasing amount of the acceptor. In mixed experiments in which liver enzyme activity was tested towards hepatoma acceptor glycoproteins, a gradual drop in sialyltransferase activity occurred with increasing quantities of the acceptor. This effect seems to be a consequence of the presence of some inhibitor in the microsomal fractions from the hepatoma cells.
Cancer Biochem Biophys 1990 Nov
PMID:Partial characterization of microsomal sialyltransferase from chicken liver and hepatoma Mc-29: II. Measurement of enzyme activities utilizing microsomal glycoproteins as exogenous acceptors. 208 39


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