Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Levels of plasma sialyltransferase were measured in a patient with disseminated carcinoma of the testes. Initial enzyme values, elevated six fold above those in normal controls, were among the highest thus far encountered in a population of patients with various stages and types of malignancy. During a remarkable respose to chemotherapy with cis-diaminodichloroplatinum, plasma sialyltransferase levels fell markedly. Serial measurement of this enzyme may aid in evaluation of tumor responsiveness to therapy in patients whose disease is not readily measurable.
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PMID:Alterations in plasma sialyltransferase associated with successful chemotherapy of a disseminated tumor. Case report. 99 Nov 25

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.
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PMID:Sialyltransferase activity and hepatic tumor growth in a nude mouse model of colorectal cancer metastases. 131 99

Changes in the glycosylation of asparagine-linked oligosaccharides have been shown in various tumor cells, including human colon cancer. Attempts were made to elucidate the difference in Asn-linked oligo-saccharides attached to lysosomal membrane glycoproteins isolated from sublines of human colon carcinoma exhibiting high and low metastatic potentials in nude mice. Lysosomal membrane glycoproteins (lamp) 1 and 2 were immunoprecipitated from the cells after labeling with radioactive sugars, and the glycopeptides prepared were fractionated by serial lectin affinity chromatography employing immobilized concanavalin A, Datura stramonium agglutinin, and tomato lectin. Comparison of Asn-linked oligosaccharides from the different colonic carcinoma cells revealed the following features. First, the highly metastatic carcinoma cells express more poly-N-acetyllactosaminyl side chains with branched galactose residues than cells with low metastatic potential. Second, sialylation is more significant in the highly metastatic carcinoma cells than in the poorly metastatic ones. Conversely, N-acetyllactosamine units are less fucosylated in the highly metastatic cells than in poorly metastatic cells. These structural changes were apparently caused by the increase in sialyltransferase and the decrease in alpha 1----3 fucosyltransferase in the highly metastatic cells. The results also suggest that highly metastatic carcinoma cells express more sialyl Lex structures at the termini of poly-N-acetyllactosaminyl side chains than poorly metastatic carcinoma cells. Further, highly metastatic cells were found to express more lamp-1 and lamp-2 on the cell surface. These results were found to be correlated to the increased expression of sialyl Lex structures with high affinity binding of anti-sialyl Lex antibody on highly metastatic cells. Increased expression of sialyl Lex in the poly-N-acetyllactosamines of the cell surface may contribute to the metastatic behavior of the cells, assuming that this structure can serve as a better ligand for selectins present on endothelial cells and platelets.
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PMID:Differential glycosylation and cell surface expression of lysosomal membrane glycoproteins in sublines of a human colon cancer exhibiting distinct metastatic potentials. 154 42

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.
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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.
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PMID:Enhanced expression of ganglioside GD3 in human and rat hepatocellular carcinoma cells and NIH 3T3 cells transfected with human tumor DNAs. 170 52

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.
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PMID:Immunohistochemical expression of blood group substances and related carbohydrate antigens in breast carcinoma. 190 2

The expression of antigens of the blood group Lewis a/b family were studied in a series of 42 prostatectomy specimens from patients with adenocarcinoma clinically confined to the prostate; 19 of these were later reclassified as pathologic Stage C. Staining of normal or hyperplastic versus neoplastic epithelium was assessed in routinely processed, paraffin-embedded tissue using murine monoclonal antibodies and an avidin-biotin immunoperoxidase technique. Antigens screened and the antibodies used to recognize them were Lewis a (CF4C4), Lewis b and Type 1 H (NS10), monosialosyl Lewis a I (19.9), and disialosyl Lewis a and monosialosyl Lewis a II (FH7). FH7 strongly stained the benign epithelium of all 39 Lewis positive cases, suggesting that the sialyltransferase responsible for synthesis of FH7-reactive determinants is highly active in benign prostatic tissue. When compared to the reactivity of benign epithelium in Lewis positive cases, the staining of the carcinomas was markedly reduced in 18 cases (46%) and absent in 16 cases (41%). This reduction or loss of staining of the malignant epithelium was observed for all antibodies that stained the corresponding benign epithelium of each case. In only five of the cases (13%) was the intensity of staining in the carcinoma equal to that of the surrounding benign epithelium. No cases in this latter group had recurrence of disease, whereas in the other staining groups 25-33% of the cases had recurrences; median follow-up for the entire group was 78 months. No correlation was apparent between Gleason score and the staining pattern with these antigens. In summary, antigens of the Lewis a/b family are deleted in a high percentage of cases of prostatic adenocarcinoma.
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PMID:Deletion of antigens of the Lewis a/b blood group family in human prostatic carcinoma. 245 82

Galactosyltransferase (GalTF), sialyltransferase (SiaTF), fucosyltransferase (FucTF), 5'-nucleotidase (5'Nucl), and ADP-ribosyltransferase (RibTF) were determined in three subcellular fractions of tumor cells and adjacent control tissue from 20 patients with small primary infiltrating ductal adenocarcinomas of the breast. Viable, as pure tumor cell populations as possible were isolated, subfractionated, and their enzyme levels compared to those in the patients' sera. The activities in tumor cells of the three glycosyltransferases were two- to seven-fold higher, whereas 5'-Nucl and RibTF showed reduced activities when compared to adjacent noninvolved tissue. Serum GalTF and SiaTF were slightly elevated in early mammary carcinoma, whereas FucTF, 5'Nucl, and RibTF were decreased in comparison with a control group. The proposed tumor origin of circulating enzymes could not be confirmed. Surprisingly, only for RibTF could a correlation between tumor and serum activity be established; a weak correlation was found for SiaTF. However, no such relationship could be determined for GalTF, FucTF, or 5'Nucl. In conclusion, the enzyme profile of the tumor cell does not, except for RibTF, appear in the serum. Serum enzyme profiles, therefore, do not permit detection of the early stages of breast cancer. A high correlation between RibTF activity and cytosol estrogen and progesterone receptor levels has been determined in tumor cells, possibly indicating slower growing, more differentiated types of breast tumors.
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PMID:Enzyme activities in human breast tumor cells and sera. 299 19

Purified lactotetraosylceramide (Gal beta 1----3GlcNAc beta 1----3Gal beta 1----4Glc1-Cer) was tested for its ability to accept [14C]sialic acid from CMP-[14C]sialic into monosialoganglioside fractions in the presence of membrane fractions purified from human colorectal carcinoma cells (SW1116). Membrane fractions were isolated by three different methods: sucrose density centrifugation, CMP-agarose gel column chromatography, and LcOse4 gel chromatography. We optimized the incubation conditions for detergent dependency (taurocholate), pH (6.3), and acceptor concentration. The sialyltransferase activity was dependent on membrane protein and linear for time up to at least 4 h. The LcOse4 affinity chromatography of the crude microsomal membrane pellet from these cells yielded a membrane fraction that was 136-fold enriched in LcOse4 acceptor specific activity compared to cell homogenates. The apparent Km for the sialyltransferase activity with LcOse4Cer acceptor in the presence of affinity-purified membranes was 20 microM and the Vmax was 7 pmol h-1 (100 micrograms of protein)-1. Acceptor capabilities of other core structures were 5-20-fold lower: LcOse4Cer much greater than GgOse4Cer greater than nLcOse4Cer much greater than GbOse4Cer. The enzymatic activity was purified further (900-fold) by a combination of LcOse4 and CMP affinity gels. SDS-PAGE electrophoresis of this material showed a major set of closely migrating bands of Mr 58,000-54,000 compared to authentic proteins, as well as a minor band at 27,000. We analyzed picomole quantities of the radioactive product by convenient controlled short-term hydrolyses with an endoglycoceramidase and sialidases (from four different sources) in comparison to sialylated tetrasaccharides of known structure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Purification and characterization of a CMP-sialic:LcOse4Cer sialyltransferase from human colorectal carcinoma cell membranes. 306 17

Serum sialyltransferases and fucosyltransferases measured by an affinity adsorbent technique were studied in 27 exactly defined patients with malignant pulmonary diseases. Fourteen patients with benign pulmonary diseases and 56 with benign surgical diseases were used as controls. Enzyme activities were expressed as amounts of labeled precursor molecules incorporated into endogenous acceptors in counts per minute (cpm). The mean sialyltransferase activity was 583 cpm in bronchial carcinoma, 485 cpm in benign pulmonary disease and 428 cpm in benign surgical disease. The only statistically significant difference was between bronchial carcinoma and benign surgical disease. The mean fucosyltransferase activity was 813 cpm in bronchial carcinoma, 436 cpm in benign pulmonary disease and 255 cpm in benign surgical disease. All the differences were statistically significant. There were no statistically significant differences between the WHO histologic bronchial carcinoma groups. The correlation between sialyltransferase and fucosyltransferase activity in bronchial carcinoma was statistically significant (r = 0.59). In squamous cell carcinoma (N = 6), it was strongly significant (r = 0.96) and there was a significant correlation also in small cell carcinoma (N = 10; r = 0.79) but not in adenocarcinoma (N = 9; r = 0.30) and benign pulmonary disease (N = 14; r = 0.44). It is suggested that serum sialyltransferases and fucosyl transferases would not be decisive for diagnosis when used alone in bronchial carcinoma, but could be included in a screening test battery.
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PMID:Serum sialyltransferase and fucosyltransferase activities in patients with bronchial carcinoma. 631


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