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:2.4.99.6 (sialyltransferase)
1,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The correlation between levels of sialic acid and sialic acid-containing glycolipids (gangliosides) in tumors and serum with the growth characteristics of the tumors was investigated in transplantable hepatomas and squamous cell carcinomas initiated with the carcinogen N-2-fluorenylacetamide and propagated in vivo and in tissue culture. Tumor lines varied in histologic classification, growth rate, and ability to form pulmonary metastases. There was neither a correlation between growth rate and histologic classification nor between either of these two parameters and the ability to metastasize. Total and ganglioside sialic acid levels were elevated in carcinogen-treated liver and in transplantable hepatomas when contrasted with normal liver. Levels of sialic acid showed a weak correlation with the growth rate of hepatomas. Gangliosides from nonmetastatic hepatoma lines exhibited less N-acetylneuraminic acid--galactose--glucose-N--acylsphingosine (GM3) and an increased ratio of total monosialogangliosides to disialogangliosides than did metastatic lines. Ganglioside patterns of metastatic hepatoma lines more closely resembled the ganglioside patterns of normal liver than did those of the nonmetastatic lines. Concomitant elevations of total and ganglioside sialic acid levels were observed in sera of animals bearing subcutaneous implants. Serum levels of total sialic acid did correlate with total sialic acid levels found in the tumor tissues. The levels of serum sialic acid were not correlated directly with levels of serum sialyltransferase activity. Elevations of both tissue and serum ganglioside sialic acid were consistent features of liver tumorigenesis in the rat after N-2-fluorenylacetamide administration. They appeared, furthermore, to be early events not directly related to tumor cell differentiation or metastasis.
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PMID:Characteristics of transplantable tumors induced in the rat by N-2-fluorenylacetamide: elevations in tissue and serum sialic acid. 692 77

The activities of the sialyltransferase enzymes and the resulting expression of sialoglycoproteins were examined in tumor cells derived from different tissues in order to gain a greater understanding of the factors controlling the cell glycosylation state. Cell-cell contact, which is dependent on cell confluency state, was shown to influence glycosylation in the neurally-derived mouse neuro-2A neuroblastoma and the C6 glioma cell lines. Both showed a relatively high level of cell sialyltransferase activity under sub-confluent conditions with activity decreasing upon the formation of cell-cell contacts associated with confluency. A parallel decrease in the expression of sialoglycoproteins, as determined by lectin blot analysis, was observed under these conditions. In contrast, the H411e hepatoma cell line showed an increase in enzyme activity with confluency with the susceptibility of the enzyme in this cell line to glucocorticoid induction only being detected in sub-confluent cell cultures. The number of trypsinisation cycles of the cells was also shown to affect the enzyme activity of the neuro-2A and C6 cells with an increase in enzyme activity coincident with passage number being observed in the neuro-2A cells, and a decrease in the C6 glioma cell line. Trypsinisation had no effect on enzyme activity in the H411e cells. These results demonstrate that the control of sialyltransferase activity in tumor cells is multifactorial with the tissue of origin playing a key role.
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PMID:The control of sialyltransferase activity in tumor-cell lines derived from different tissues in multifactorial. 764 68

The human beta-galactoside alpha 2,6-sialyltransferase (EC 2.4.99.1) (SiaT-1) gene is localized to human chromosome 3 (q21-q28) by Southern analysis of somatic cell hybrids and by in situ hybridization of metaphase chromosomes. Comparative analysis between the human and the previously reported rat SiaT-1 genomic sequences demonstrates precise conservation of the intron/exon boundaries throughout the coding domains. Furthermore, there is extensive inter-species sequence similarity in some of the exons that contain information only for the 5'-leader regions. Human genomic sequences were also analyzed to reconcile reported differences in the 5'-untranslated region in SiaT-1 mRNAs. In cultured cell lines of the B-lineage, Reh, Nalm-6, Jok-1, Ball-1, Daudi, and Louckes, the study demonstrates that three upstream exons, Exons(Y+Z) and Exon(X), are mutually exclusively utilized, resulting in at least two distinct populations of SiaT-1 mRNA being synthesized. None of these exons is present in the SiaT-1 mRNA isotype expressed in HepG2 human hepatoma cells. In all B-lymphoblastoid cell lines examined, the basal level SiaT-1 mRNA is maintained by the expression of an isotype containing the Exons(Y+Z) sequence. The slightly smaller SiaT-1 mRNA, which contains the Exon(X) sequence but not Exons(Y+Z) sequence, is synthesized at a high level and found only in Jok-1, Daudi, and Louckes, the cell lines with mature B-cell phenotype. The study also provides further evidence that induced SiaT-1 expression accompanies the appearance of CDw75, a putatively sialylated cell surface epitope and a marker of human mature B-lymphocytes. The SiaT-1 induction is the result of the appearance of a novel form of SiaT-1 mRNA isotype.
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PMID:Chromosome mapping and organization of the human beta-galactoside alpha 2,6-sialyltransferase gene. Differential and cell-type specific usage of upstream exon sequences in B-lymphoblastoid cells. 778 24

Tumor cell surface sialic acid levels determine a number of important properties governing cellular interactions and cell-cell communication. Towards understanding the mechanism of regulation of sialic acid levels upon cellular transformation, we have studied the regulation of expression of beta-galactoside alpha 2,6-sialyltransferase in a rat tumor, the Zajdela ascitic hepatoma. We demonstrate distinct differences in the regulation of expression of the enzyme in the tumor cells as compared to normal liver cells. The expression of sialyltransferase is regulated both at the transcriptional and post-transcriptional level in a tissue-specific manner.
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PMID:Regulation of expression of beta-galactoside alpha 2,6-sialyltransferase in a rat tumor, Zajdela ascitic hepatoma. 842 23

Comparative studies on the content of sialic acid and on the sialyltransferase activity in normal serum and in serum of rats with Zajdela ascitic hepatoma in different phases of tumor development have been conducted. Unlike the serum from animals with tumors, in which the sialic acid quantity increases in dependence of the stage of tumor development, the activity of serum sialyltransferase statistically augmented only in serum of rats at the final stage of tumor progression. The sialyltransferase activity towards asialofetuin as an acceptor in normal liver and in Zajdela hepatoma cells, was measured and a decrease in this activity in tumor cells as well as in host liver was found. When lactose was used as acceptor, again lower enzyme activity in the tumor cells in comparison with that in liver was established, but in liver and in hepatoma cells the predominant 14C-labelled product of the sialyltransferase assay was alpha (2-6) sialyllactose isomer. The results contribute to the biochemical characterization of rat Zajdela hepatoma.
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PMID:Activity and characterization of sialyltransferase from serum of normal rats, of rats bearing Zajdela ascitic hepatoma, in normal host liver and in Zajdela hepatoma cells. 884 9

Previous studies have demonstrated sialyltransferase (ST) enzyme activity to be induced in hepatic cells by corticosteroids. In this study, we used the H411e rat hepatoma cell line to further characterise this induction with particular reference to the subsequent changes in the pattern of sialoglycoprotein (SGP) expression. The induction of total ST activity by dexamethasone was concentration dependent with maximum induction occurring 12 h subsequent to drug addition. Western blot analysis demonstrated that the induction was associated with an increase in the expression of the alpha2,6(N) ST enzyme with no change in the expression levels of the alpha2,3(N) enzyme. While the induction resulted in an increase in the reaction velocity (Vmax) of the enzyme for both the sugar donor (CMP-Neu5Ac) and the asialofetuin acceptor protein, there was no significant change in the enzyme affinity (Km) for the substrates, suggestive of either an increase in the expression or efficiency of the existing enzyme(s) rather than an induction of novel ST enzymes. Lectin blot analysis of cellular glycoprotein expression demonstrated no change in the expression patterns of either alpha2,3 or alpha2,6-linked SGP following enzyme induction. These results suggest that the available acceptor sites for the terminal sialic acid group(s) may be fully occupied in the control cells and therefore there are no further sites onto which the sialic acid can be transferred following induction of ST enzyme activity. This may be due to the high basal enzyme levels in the control cells already exhausting endogenous acceptor sites.
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PMID:The biochemical consequences of alpha2,6(N) sialyltransferase induction by dexamethasone on sialoglycoprotein expression in the rat H411e hepatoma cell line. 928 Mar 18

A single gene, SIAT1, encodes ST6Gal I, the sialyltransferase that mediates transfer of alpha2,6-linked sialic acids to Galbeta1, 4GlcNAc termini of N-linked glycoproteins. In vivo, multiple SIAT1 mRNA forms, differing only in the 5'-untranslated region, are expressed in a tissue-specific manner. This mRNA heterogeneity has been attributed, at least in part, to transcription from a number of physically distinct promoter regions. In mature B-lymphocytes, SIAT1 transcription initiates at P2, a regulatory region known to function only in B-lineage cells. Bacterial chloramphenicol acetyltransferase (CAT) under the control of the P2 region encompassing 415 bp 5'- and 125 bp 3' of the transcriptional initiation site is efficiently expressed in Louckes, a mature B-lymphoblastoid cell line. In contrast, CAT expression in Reh, a T-null/B-null precursor line, and in HepG2, a hepatoma line, are 14-fold and >25-fold less than in Louckes, respectively. The data is consistent with the presence of cis -acting regulatory elements residing both 5' and 3' of the P2 transcriptional initiation site. At least 370 bp of 5'-flanking sequence, coinciding with the inclusion of AP2 and NF-kappaB sites, is necessary for high level expression in Louckes. Exon sequences 3' of the transcription start site are also important for expression. A segment from(+)32 to(+)125 (position(+)1 is transcription start site) is capable of exerting promoter-like activity in Louckes, but not in Reh or HepG2. CAT expression by P2 is negligible in Reh cells. However, enhanced CAT activity is not accompanied by elevated mRNA levels. This observation is consistent with the relief of translational restraints imposed by the(+)32 to(+)125 region. Together, the data demonstrate that efficient and cell-specific transcription regulation in mature B lymphocytes is contained in a 495 bp P2 segment that is comprised of 370 bp of 5'-flanking region and 125 bp of transcribed region of Exon X.
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PMID:Transcription of the beta-galactoside alpha2,6-sialyltransferase gene (SIAT1) in B-lymphocytes: cell type-specific expression correlates with presence of the divergent 5'-untranslated sequence. 1046 Aug 32

The major alpha1,3fucosyltransferase activity in plasma, liver, and kidney is related to fucosyltransferase VI which is encoded by the FUT6 gene. Here we demonstrate the presence of alpha1, 3fucosyltransferase VI (alpha3-FucT VI) in the human HepG2 hepatoma cell line by specific activity assays, detection of transcripts, and the use of specific antibodies. First, FucT activity in HepG2 cell lysates was shown to prefer sialyl-N-acetyllactosamine as acceptor substrate indicating expression of alpha3-FucT VI. RT-PCR analysis further confirmed the exclusive presence of the alpha3-FucT VI transcripts among the five human alpha3-FucTs cloned to date. alpha3-FucT VI was colocalized with beta1,4galactosyltransferase I (beta4-GalT I) to the Golgi apparatus by dual confocal immunostaining. Pulse/chase analysis of metabolically labeled alpha3-FucT VI showed maturation of alpha3-FucT VI from the early 43 kDa form to the mature, endoglycosidase H-resistant form of 47 kDa which was detected after 2 h of chase. alpha3-FucT VI was released to the medium and accounted for 50% of overall cell-associated and released enzyme activity. Release occurred by proteolytical cleavage which produced a soluble form of 43 kDa. Monensin treatment segregated alpha3-FucT VI from the Golgi apparatus to swollen peripheral vesicles where it was colocalized with beta4-GalT I while alpha2,6(N)sialyltransferase remained associated with the Golgi apparatus. Both constitutive secretion of alpha3-FucT VI and its monensin-induced relocation to vesicles analogous to beta4-GalT I suggest a similar post-Golgi pathway of both alpha3-FucT VI and beta4-GalT I.
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PMID:alpha1,3Fucosyltransferase VI is expressed in HepG2 cells and codistributed with beta1,4galactosyltransferase I in the golgi apparatus and monensin-induced swollen vesicles. 1053 43

Caveolin-1 is a major structural protein of caveolae and plays important functions in tumorigenesis and development. Hca-F and Hepa1-6 are mouse hepatocarcinoma cell lines with high and low malignant potential, respectively. Our previous studies revealed that caveolin-1 promoted cell invasion by up-regulating the glycosylation of matrix metalloproteinase inducer CD147 of Hepa1-6 and Hca-F cells. However, the roles of caveolin-1 in cell-ECM adhesion and the mechanisms involved remain unknown. This study showed that caveolin-1 overexpression in Hepa1-6 cells up-regulated sialyltransferase ST6Gal-I expression and activated FAK-mediated adhesion signaling, and down-regulation of ST6Gal-I attenuated caveolin-1-induced increase in the adhesive ability of Hepa1-6 cells to fibronectin. Conversely, caveolin-1 knockdown in Hca-F cells inhibited ST6Gal-I expression and FAK signaling-mediated cell adhesion to fibronectin. Re-expression of wild-type caveolin-1 or ST6Gal-I rescued the decreased ST6Gal-I expression and adhesion of Hca-F cells caused by caveolin-1 silencing. Further studies indicated that caveolin-1 might regulate ST6Gal-I expression through caveolin-1 scaffolding domain. Taken together, these results demonstrate for the first time that caveolin-1 can up-regulate ST6Gal-I expression and further contribute to promoting mouse hepatocarcinoma cell adhesion to fibronectin by activating FAK-mediated adhesion signaling.
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PMID:Caveolin-1 up-regulates ST6Gal-I to promote the adhesive capability of mouse hepatocarcinoma cells to fibronectin via FAK-mediated adhesion signaling. 2302 90

Aberrant sialylation is closely associated with malignant phenotypes of tumor cells, including invasiveness and metastasis. This study investigated sialylation with regard to the modification of invasive properties and chemosensitivity in human hepatocellular carcinoma (HCC) cell lines and the association between the sialyltransferase gene family and clinicopathological characteristics in HCC patients. Using mass spectrometry analysis, we found that the composition profiling of sialylated N-glycans differed between MHCC97H and MHCC97L cells with different metastatic potential. The expressional profiles of 20 sialyltransferase genes showed differential expression in two cell lines, transitional and tumor tissues, from the same patients. Two genes, ST6GAL1 and ST8SIA2, were detected as overexpressed in MHCC97H and MHCC97L cells. The altered expression levels of ST6GAL1 and ST8SIA2 corresponded to a changed invasive phenotype and chemosensitivity of MHCC97H and MHCC97L cells both in vitro and in vivo. Further data indicated that manipulation of the expression of the two genes led to altered activity of the phosphoinositide-3 kinase (PI3K)/Akt signaling pathway. Targeting the PI3K/Akt pathway by its specific inhibitor wortmannin or by Akt RNA interference resulted in a reduced capacity for invasion and chemoresistance of MHCC97H cells. Our results imply that sialylation may function as an internal factor, regulating the invasion and chemosensitivity of HCC, probably through ST6GAL1 or ST8SIA2 regulation of the activity of the PI3K/Akt pathway.
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PMID:Modification of sialylation mediates the invasive properties and chemosensitivity of human hepatocellular carcinoma. 3115 39


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