Disease relevance of ST3GAL4

• Clinical significance of ST3Gal IV expression in human renal cell carcinoma [1].
• A multiplex reverse transcription-PCR method was used here to determine the expression of five sialyltransferases (ST3Gal III, ST6Gal I, ST3Gal IV, ST3Gal I, and ST3Gal II) in 49 patients surgically treated for locoregional breast cancer [2].
• The other genes, Fuc-TIII, Fuc-TVI, and ST3Gal IV, which were most abundantly expressed in colorectal tissues, did not show significant up-regulation except in the poorly differentiated carcinomas [3].
• Based on the levels of transcripts of the 12 enzymes together with the amounts of sialyl Lewis antigens, we concluded that Fuc-TIII, Fuc-TVI, and ST3Gal IV are mainly responsible for synthesis of the sialyl Lewis antigens in colon tissues, but are not responsible for the augmented expression of the antigens in colorectal cancers [3].
• They had higher ST3Gal IV expression than patients without pulmonary hypertension (0.73 vs 0.29, p = 0.04) and a higher ST3Gal IV/ST6Gal I ratio than patients without pulmonary hypertension (1.03 vs 0.27, p = 0.03) and controls (1.03 vs 0.28, p = 0.02) [4].

High impact information on ST3GAL4

• Mucopolysaccharidosis type IVA (MPS IVA) results from a genetic deficiency of N-acetylgalactosamine-6-sulfate (Gal-NAc6S) sulfatase [5].
• Furthermore, the expression of a RD29A-LUC reporter gene is repressed significantly by STZ/ZAT10 in transient expression assays in Arabidopsis leaves [6].
• Evidence is provided that high-TNFalpha-producing clones generated from a human lymphoma T-cell line (ST4) can undergo apoptosis following transduction of the TNFalpha gene [7].
• We show here that all SIA-nu/nu mice engrafted intravenously with 5 x 10(6) malignant lymphoblasts originally derived from a child with a T-cell acute lymphoblastic leukemia (PF382) and from a boy with a T-cell lymphoma (ST-4) develop lethal meningeal leukemia and die within 35 days [8].
• Polymorphonuclear cells (PMNs) exposed to PMN7C3 show a significant depression in O2- release (52.8% +/- 2.5% of control), H2O2 release (44.4% +/- 6.0% of control), and O2 consumption (73.9% +/- 2.6% of control) in response to STZ [9].

Chemical compound and disease context of ST3GAL4

• Hematologic toxicity was similar for both treatments; however, the 5-FU plus STZ patients experienced more vomiting but acceptable renal toxicity [10].
• FU/STZ improved survival compared with the doxorubicin-based regimen, suggesting that the combination should be considered to be an active regimen of therapy when chemotherapy is judged to be an option for selected patients with carcinoid tumors [11].
• PATIENTS AND METHODS: Two hundred forty-nine patients with advanced carcinoid tumors were randomized to either doxorubicin with fluorouracil (FU/DOX) or streptozocin with fluorouracil (FU/STZ) [11].
• Patients crossed over to the dacarbazine (DTIC) treatment after disease progression following first-line treatment (either FU/DOX or FU/STZ), and 73 patients were assigned to one of these three treatments based on their previous treatment or on abnormal baseline cardiac or renal function [11].
• Relative to STZ-injected controls, P32/98-treated animals displayed increased weight gain (230%) and nutrient intake, decreased fed blood glucose ( approximately 26 vs. approximately 20 mmol/l, respectively), and a return of plasma insulin values toward normal (0.07 vs. 0.12 nmol/l, respectively) [12].

Biological context of ST3GAL4

• These results indicate that down-regulation of ST3Gal IV mRNA may be one of the factors associated with the malignant progression of human RCC [1].
• ST3Gal IV cDNA obtained by polymerase chain reaction from cDNA library of human RCC cell line ACHN was identical to STZ in nucleotide sequence [1].
• Four genes, ST3Gal I, ST6Gal I, beta1,4GalT, and Core2 GnT, showed a tendency toward up-regulation, and a ST3Gal III gene showed a tendency toward down-regulation [3].
• IL-1beta-induced sLeX expression on HuH-7 cells was suppressed by transfection of gene-specific small interference RNAs against FUT VI and ST3Gal IV but not against FUT IV and ST3Gal III [13].
• Earlier work from our laboratory has shown that the respiratory burst and homotypic aggregation response in these cells induced by opsonized particles (serum-treated zymosan, STZ), is strongly enhanced after pretreatment (priming) with PAF [14].

Anatomical context of ST3GAL4

• Characterization of two glycolipid: alpha 2-3sialyltransferases, SAT-3 (CMP-NeuAc:nLcOse4Cer alpha 2-3sialyltransferase) and SAT-4 (CMP-NeuAc:GgOse4Cer alpha 2-3sialyltransferase), from human colon carcinoma (Colo 205) cell line [15].
• CONCLUSIONS: STZ mRNA and the enzyme itself are expressed in the basal layer of the corneal epithelium but are absent in the limbus [16].
• In order to characterise the candidate alpha2,3-sialyltransferases necessary for biosynthesis of the selectin ligand SLe(x) and related antigens we have cloned and sequenced, from peripheral blood leukocytes of single individuals, various transcripts from the human ST3Gal III, IV and VI genes [17].
• Low ST6Gal I expression associated with normal ST3Gal IV expression, resulting in a higher ST3Gal IV/ST6Gal I ratio, suggests an enhanced expression of Sialyl-LewisX at the surface of PBMC in SSc, and therefore an active interaction between activated endothelial cells and PBMC through the binding between E-selectin and Sialyl-LewisX [4].
• In cremaster muscle venules with or without TNF-alpha treatment, L-selectin-dependent rolling was almost completely abolished in ST3Gal-IV(-/-) mice [18].

Associations of ST3GAL4 with chemical compounds

• Characterization of the catalytic reaction products of SAT-3 and SAT-4 with thin-layer chromatography, sialidase treatment, and binding to specific antibodies indicates that both SAT-3 and SAT-4 catalyze the formation of alpha 2-3 linkage between sialic acid and terminal galactose of glycolipid substrates [15].
• Sialyltransferase activities, SAT-3 (CMP-NeuAc:nLcOse4Cer alpha 2-3sialyltransferase) and SAT-4 (CMP-NeuAc:GgOse4Cer alpha 2-3sialyltransferase), in Colo 205 cells catalyze the transfer of sialic acid to the terminal galactose of GlcNc-- and GalNAc-containing glycolipid substrates, respectively [15].
• The column eluent with SAT-3 activity failed to transfer sialic acid to asialo alpha(1)-acid glycoprotein, indicating that this enzyme is different from the sialyltransferase (ST3N) that synthesizes NeuAc alpha 2-3Gal linkage in asparagine-linked oligosaccharides of glycoprotein [15].
• Interleukin-1beta induces sialyl Lewis X on hepatocellular carcinoma HuH-7 cells via enhanced expression of ST3Gal IV and FUT VI gene [13].
• Estradiol induced a statistically significant increase in ST3Gal III and a decrease in ST6Gal I, whereas the two other enzymes, ST3Gal IV and ST3Gal I, are not modified and expression of the fifth enzyme, ST3Gal II, was very low or not detectable [19].

Regulatory relationships of ST3GAL4

• Furthermore, the inflammatory cytokine TNF could enhance some alpha 2,3-ST and alpha 1,3/1,4-FT activities capable of generating E-selectin counter-receptors [20].

Other interactions of ST3GAL4

• The gene symbols for these genes have been designated SIAT4A, SIAT4B and SIAT4C, respectively [21].
• Interestingly, all of the 12 glycosyltransferase genes examined, except the Fuc-TV, Fuc-TVI, Fuc-TVII, and ST3Gal III genes, were markedly up-regulated in all of the poorly differentiated carcinomas [3].
• In contrast to ST3Gal III and ST3Gal IV, this enzyme exhibited restricted substrate specificity, i.e. it utilized Galbeta1,4GlcNAc on glycoproteins, and neolactotetraosylceramide and neolactohexaosylceramide, but not lactotetraosylceramide, lactosylceramide, or asialo-GM1 [22].
• Transcripts of FucT-VII and core 2 GlcNAc transferase (C2GnT) were up-regulated after activation, while those of ST3GalIV and beta1-->4GalT-I were expressed constitutively [23].

Analytical, diagnostic and therapeutic context of ST3GAL4

• RESULTS: RT-PCR yielded cDNA of expected basepair length for STZ and ST3(Gal II [16].
• The 6 cases that possessed almost the same levels of ST3Gal IV mRNA in primary tumor tissues as those in non-tumor kidneys showed favorable prognoses, as assessed by Kaplan-Meier curve [1].
• Identification of nine alternatively spliced alpha2,3-sialyltransferase, ST3Gal IV, transcripts and analysis of their expression by RT-PCR and laser-induced fluorescent capillary electrophoresis (LIF-CE) in twenty-one human tissues [17].
• RESULTS: In the randomized group, there was no difference between FU/DOX and FU/STZ in response rates (15.9% v 16%) and progression-free survival (4.5 v 5.3 months) [11].
• The monoclonal antibodies also cross-reacted with the nucleocapsid proteins of simian (SA11), pig (OSU), bovine (NCDV and UK) and human (Wa and ST4) rotaviruses in an immunoblot ELISA reaction [24].

References