Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

n-Butyrate, a short chain fatty acid that is produced by colonic bacterial fermentation, is detectable in portal blood and induces differentiation in various human neoplastic cell lines. Earlier reports indicated approximately 20-fold induction in vitro by n-butyrate of the sialyltransferase that catalyzes terminal glycosylation of GM3 ganglioside in HeLa and colon cancer cells. We previously isolated a 1.3-kilobase cDNA for a human beta-galactoside alpha 2,6-sialyltransferase, for which N-linked glycoproteins are the acceptors. We report here that treatment of Hep G2 cells with 5 mM n-butyrate for 24 h reduced beta-galactoside alpha 2,6-sialyltransferase mRNA levels by approximately 90%. Reductions in mRNA level were followed by approximately 75 and approximately 90% reductions, respectively, in specific beta-galactoside alpha 2,6-sialyltransferase enzyme activity after treatment for 24 and 36 h with 5 mM n-butyrate. However, in contrast with earlier reports of enhanced ganglioside synthesis in response to n-butyrate treatment, incubation of Hep G2 cells with n-butyrate did not alter the ganglioside pattern as assessed by thin layer chromatography of lipids extracted from treated cells. Nuclear run-on reactions indicated that the rate of transcription of beta-galactoside, alpha 2,6-sialyltransferase was not altered by treatment with 5 mM n-butyrate for 24 h, but the effects of this treatment on cytoplasmic levels of beta-galactoside alpha 2,6-sialyltransferase mRNA were largely negated by co-treatment with actinomycin D or cycloheximide. Therefore, our results show that n-butyrate reduces expression of mature beta-galactoside alpha 2,6-sialyltransferase mRNA by post-transcriptional mechanisms.
 ...
PMID:n-butyrate reduces the expression of beta-galactoside alpha 2,6-sialyltransferase in Hep G2 cells. 131 8

A role of alpha 2,6-linked sialic acid in the development of an invasive phenotype in colon cancer has been suggested by several observations but never conclusively demonstrated. An experimental model to clarify this tissue was established by the creation and characterization of a bank of cell lines that differ mainly, if not exclusively, in the degree of alpha 2,6-sialylation. Human colon cancer cell lines SW48 and SW948, normally unable to elaborate the alpha 2,6-sialyl linkage, were transfected with the beta-galactoside alpha 2,6-sialyltransferase (alpha 2,6ST) cDNA driven by the cytomegaloviral promoter and screened for cell surface alpha 2,6-sialylated sugar chains using fluorescein isothiocyanate-conjugated Sambucus nigra agglutinin (SNA-FITC). A panel of SNA-FITC-positive clones was established that expresses alpha 2,6ST activity of varying degrees. Only the SNA-FITC-positive recombinants express the 1.2 Kb mRNA predicted to be generated from the transfected sequence. No 4.3-4.7 Kb transcripts that are indicative of transcription from the native alpha 2,6ST gene were detected.
 ...
PMID:Human colon cancer cell lines permanently expressing alpha 2,6-sialylated sugar chains by transfection with rat beta-galactoside alpha 2,6 sialyltransferase cDNA. 779 69

In previous works we established that the alpha 2,6-sialyltransferase acting on N-acetyllactosaminic sequences [alpha 2,6(N)ST, E.C. 2.4.99.1] behaves, in colonic cells, as an oncodevelopmentally regulated enzyme. Subpopulations of the human colon cancer cell line HT-29 adapted to grow in 10(-5) M methotrexate (MTX), permanently retain the ability to differentiate as mucus-secreting cells when kept confluent for extended periods of time [Lesuffleur et al. (1991) J. Cell Biol. 115, 1409-1418]. In this study we have compared the activities of five sialyltransferases acting on N- or O-linked chains of glycoproteins in parental HT-29 and in the 10(-5) M MTX-resistant variant. Both cell lines were studied during the exponential phase of growth as well as after a long period of postconfluent culture (28-30 days). Regardless the culture conditions, resistance to 10(-5) M MTX is associated with a virtual disappearance of alpha 2,6(N)ST activity. This change results in a dramatic reduction of the reactivity of cell membranes with the fluorescent lectin from Sambucus nigra, specific for alpha 2,6-sialylated structures. The activity of the alpha 2,3-sialyltransferase which acts on N-acetyllactosaminic sequences increases about two times in postconfluent cultures of 10(-5) M MTX-resistant cells, suggesting a close relationship with the differentiation degree. No significative changes were observed in the activity of other sialyltransferases.
 ...
PMID:Resistance to methotrexate is associated with selective changes of alpha 2,6- and alpha 2,3-sialyltransferase activities toward N-acetyllactosaminic sequences in human colon cancer cell line HT-29. 824 Mar 48

The extent of processing of N-linked oligosaccharides and the sialylation of the target cell membranes has been positively correlated with resistance to lysis mediated by NK cells, but a conclusive evidence has never been reached. Colon cancer tissues express an increased activity of beta-galactoside alpha 2,6-sialyltransferase (EC 2.4.99.1, alpha 2,6ST), which catalyzed the addition of sialic acid in alpha 2,6-linkage to Gal beta 1,4GlcNAc (N-acetyllactosamine) sequences of glycoprotein N-linked chains. The resulting increased level of membrane alpha 2,6-sialylation appears to be related with a more invasive behavior of cancer cells. This phenomenon may depend on a decreased sensitivity of colon cancer cells to NK cells. To obtain conclusive evidence on the role played by sialylation of N-linked chains in determining the target cell susceptibility to NK-mediated lysis, human colon cancer cell lines not expressing sialyltransferases acting on N-linked chains were transfected with a rat alpha 2,6ST cDNA. Stable transfectants expressed different levels of alpha 2,6ST activity, were reactive with the Sambucus nigra lectin, specific for alpha 2,6-linked sialic acid, and compared with control transfectants, showed a remarkable decrease in the number of unsubstituted Gal beta 1,4GlcNAc terminal sequences. The NK susceptibility of these clones was found to be identical to that of control transfectants, either when unstimulated- or IL-2-stimulated lymphocytes were used as effectors. Neuraminidase treatment of target cells does not result in significant changes to NK susceptibility. Our data demonstrate that sialic acid alpha 2,6-linked to N-linked chains of target cell glycoproteins does not play a major role in recognition of the target by human NK cells.
 ...
PMID:Expression of beta-galactoside alpha 2,6-sialyltransferase does not alter the susceptibility of human colon cancer cells to NK-mediated cell lysis. 918 31

Transfer of terminal alpha 2,6-linked sialic acids to N-glycans is catalyzed by beta-galactoside alpha 2,6-sialyltransferase (ST6Gal I). Expression of ST6Gal I and its products is reportedly increased in colon cancers. To investigate directly the functional effects of ST6Gal I expression, human colon cancer (HT29) cells were transfected with specific antisense DNA. ST6Gal I mRNA and protein were virtually undetectable in six strains of transfected HT29 cells. ST6Gal activity was reduced to 14% of control (P<0.005) in transfected cells. Expression of terminal alpha 2,6- and alpha 2,3-linked sialic acids, and unmasked N-acetyllactosamine oligosaccharides, respectively, was assessed using flow cytometry and fluoresceinated Sambucus nigra, Maackia amurensis and Erythrina cristagalli lectins. Results indicated a major reduction in expression of alpha 2,6-linked sialic acids and counterbalancing increase in unmasked N-acetyllactosamines in antisense DNA-transfected cells, without altered expression of alpha 2,3-linked sialic acids or ganglioside profiles. The ability of transfected cells to form colonies in soft agar and to invade extracellular matrix material (Matrigel), respectively, in vitro was reduced by approx. 98% (P<0.0001) and more than 3-fold (P<0.005) compared to parental HT29 cells. These results indicate that N-glycans bearing terminal alpha 2,6-linked sialic acids may enhance the invasive potential of colon cancer cells.
 ...
PMID:Suppression of a sialyltransferase by antisense DNA reduces invasiveness of human colon cancer cells in vitro. 1140 50

An elevation of beta-galactoside alpha 2,6-sialyltransferase (ST6Gal.I) enzyme activity and an increased alpha 2,6-sialylation of cell membranes are among the most prominent glycosylation changes associated with colon cancer; both modifications correlate with a worse prognosis. In our previous studies, we have frequently observed a discrepancy between the ST6Gal.I level within a colon cancer sample or cell line and the respective level of reactivity with the alpha 2,6-sialyl-specific lectin from Sambucus nigra (SNA). In this study, we have investigated quantitatively the biosynthesis of the sialyl-alpha 2,6-lactosaminyl epitope in two colon cancer cell types expressing the ST6Gal.I cDNA under the control of a constitutive promoter. By measuring the amount of ST6Gal.I mRNA using competitive RT-PCR, the expression of alpha 2,6-sialylated lactosaminic structures with SNA and anti-CDw75 Ig, and the presence of unsubstituted lactosaminic termini by Erythrina cristagalli lectin, we reached the following conclusions: (a) a high proportion of the cell surface lactosaminic termini remains unsubstituted, even in the presence of a very high ST6Gal.I activity. This proportion is strongly dependent on the cell type; (b) ST6Gal.I-transfected colon cancer cells do not express the CDw75 epitope; (c) the level of ST6Gal.I enzyme activity only partially correlates with the mRNA level; (d) despite the control by a constitutive promoter, the ST6Gal.I mRNA is not constantly expressed over time; and (e) a very large portion of the enzyme molecules is secreted in the extracellular milieu. These results indicate that post-transcriptional and post-translational mechanisms play a pivotal role in the control of alpha 2,6-sialylation in colon cancer cells.
 ...
PMID:Biosynthesis of the cancer-related sialyl-alpha 2,6-lactosaminyl epitope in colon cancer cell lines expressing beta-galactoside alpha 2,6-sialyltransferase under a constitutive promoter. 1172 75