Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17931 (galectin-3)
 2,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Helicobacter pylori (H. pylori) infection leads to gastroduodenal inflammation, peptic ulceration and gastric carcinoma. H. pylori may induce disease-specific gene expression in gastric epithelial cells. cDNA microarray for 352 cancer-related genes was used to identify the genes altered by H. pylori (cagA positive) in gastric epithelial AGS cells. Expressions of the genes identified on the microarray and other genes closely associated with these genes were determined by reverse transcriptase-polymerase chain reaction (RT-PCR). Western blot analysis and cell adhesion assay were performed to confirm the protein levels of the genes and the role of the genes on cell adhesion in H. pylori-infected AGS cells. As a result, the expression of four genes (galectin 1, aldolase A, integrin alpha5, LIM domain only 7 (LMO7)) were up-regulated by H. pylori in AGS cells, determined by cDNA microarray. RT-PCR analysis showed that the genes up-regulated by H. pylori were the genes regulating cell-cell adhesion and cell-extracellular matrix interaction, such as galectin-1 and galectin-3, integrin alpha5, and LIM domain only 7 (LMO7), and cancer-related glycolytic enzyme aldolase A and C. Cell adhesion to extracellular matrix proteins such as poly-L-lysine and fibronectin was mediated by H. pylori-induced expression of integrin alpha5. RT-PCR and Western blot analysis showed that E-cadherin, regulating cell adhesion and contact cell inhibition, was decreased by H. pylori in AGS cells. In conclusion, the increased expression of cell adhesion molecules and decrease in E-cadherin expression by H. pylori might contribute to cell adhesion, invasion and possibly cell proliferation in gastric epithelial cells.
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PMID:Cell adhesion-related gene expression by Helicobacter pylori in gastric epithelial AGS cells. 1275 65

Earlier work described the cloning of a gene from murine 3T3 cells encoding a cytoplasmic protein Chrp containing a cysteine- and histidine-rich motif characteristic of Zn-finger proteins. The interaction of Chrp with murine galectin-3 first became evident in a yeast two-hybrid screen, but it was also observed in co-precipitation experiments from 3T3 cell lysates. Here, the formation of equimolar complexes by murine Chrp and hamster galectin-3 is shown. Moreover, we found that Chrp binds to the carbohydrate-recognition domain (CRD) of hamster galectin-3 and not to the N-terminal domain carrying the proline- and glycine-rich repeats characteristic of galectin-3 and absent in other galectins. However, galectin-1 does not bind to Chrp, although its CRD is homologous to the galectin-3 CRD. Finally, we report that galectin-3, in a complex with Chrp, binds to laminin in surface plasmon resonance experiments with similar kinetics and affinity as it does in the free state. The formation of higher-order complexes containing these proteins and additional binding partners may be relevant to cytoplasmic functions involving galectin-3.
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PMID:Specificity of interactions of galectin-3 with Chrp, a cysteine- and histidine-rich cytoplasmic protein. 1276 88

Cell surface glycans present docking sites to endogenous lectins. With growing insight into the diversity of lectin families it becomes important to answer the question on the activity profiles of individual family members. Focusing on galectins (beta-galactoside-binding proteins without Ca(2+)-requirement sharing the jelly-roll-like folding pattern), this study was performed to assess the potency of proto-type galectins (galectins-1 and -7 and CG-16) and the chimera-type galectin-3 to elicit selected cell responses by carbohydrate-dependent surface binding and compare the results. The galectins, except for galectin-1, were found to enhance detergent (SDS)-induced hemolysis of human erythrocytes to different degrees. Their ability to confer increased membrane osmofragility thus differs. Aggregation of neutrophils, thymocytes and platelets was induced by the proto-type galectin-1 but not -7, by CG-16 and also galectin-3. Cell-type-specific quantitative differences and the importance of the fine-specificity of the galectin were clearly apparent. In order to detect cellular responses based on galectin binding and bridging of cells the formation of haptenic-sugar-resistant (HSR) intercellular contacts (an indicator of post-binding signaling) was monitored. It was elicited by CG-16 and galectin-1 but not galectin-3, revealing another level at which activities of individual galectins can differ. Acting as potent elicitor of neutrophil aggregation, CG-16-dependent post-binding effects were further analyzed. Carbohydrate-dependent binding to the neutrophils' surface led to a sustained increase of cytoplasmic Ca2+ concentration in a dose-dependent manner. The ability of CG-16 to activate H2O2 generation by human peripheral blood neutrophils was primed by the Ca(2+)-ionophor ionomycin and by cytochalasin B. In a general context, these results emphasize that--besides plant lectins as laboratory tools--animal lectins can trigger cell reaction cascades, implying potential in vivo relevance for the measured activities. Within the family of galectins, the activity profiles depend on the target cell type and the individual galectin. Notably, proto-type galectins do not necessarily share a uniform capacity as elicitor.
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PMID:Analysis of selected blood and immune cell responses to carbohydrate-dependent surface binding of proto- and chimera-type galectins. 1296 52

The extracellular functions of galectin-7 (p53-induced gene 1) are largely unknown. On the surface of neuroblastoma cells (SK-N-MC), the increased GM1 density, a result of upregulated ganglioside sialidase activity, is a key factor for the switch from proliferation to differentiation. We show by solid-phase and cell assays that the sugar chain of this ganglioside is a ligand for galectin-7. In serum-supplemented proliferation assays, galectin-7 reduced neuroblastoma cell growth without the appearance of features characteristic for classical apoptosis. The presence of galectin-3 blocked this effect, which mechanistically resembles that of galectin-1. By virtue of carbohydrate binding, galectin-7 thus exerts neuroblastoma growth control similar to galectin-1 despite their structural differences. In addition to p53-linked proapoptotic activity intracellularly, galectin-7, acting as a lectin on the cell surface, appears to be capable of reducing cancer cell proliferation in susceptible systems.
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PMID:Homodimeric galectin-7 (p53-induced gene 1) is a negative growth regulator for human neuroblastoma cells. 1367 66

Galectin-3 is unique among the galectin family of animal lectins in its biological activities and structure. Most members of the galectin family including galectin-1 possess apoptotic activities, whereas galectin-3 possesses anti-apoptotic activity. Galectin-3 is also the only chimera type galectin and consists of a nonlectin N-terminal domain and a C-terminal carbohydrate-binding domain. Recent sedimentation equilibrium and velocity studies show that murine galectin-3 is a monomer in the absence and presence of LacNAc, a monovalent sugar. However, quantitative precipitation studies in the present report indicate that galectin-3 precipitates as a pentamer with a series of divalent pentasaccharides with terminal LacNAc residues. Furthermore, the kinetics of precipitation are fast, on the order of seconds. This indicates that although the majority of galectin-3 in solution is a monomer, a rapid equilibrium exists between the monomer and a small percentage of pentamer. The latter, in turn, precipitates with the divalent oligosaccharides, resulting in rapid conversion of monomer to pentamer by mass action equilibria. Mixed quantitative precipitation experiments and electron microscopy suggest that galectin-3 forms heterogenous, disorganized cross-linking complexes with the multivalent carbohydrates. This contrasts with galectin-1 and many plant lectins that form homogeneous, organized cross-linked complexes. The results are discussed in terms of the biological properties of galectin-3.
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PMID:Galectin-3 precipitates as a pentamer with synthetic multivalent carbohydrates and forms heterogeneous cross-linked complexes. 1467 41

The carbohydrate binding specificities of the galectin family of animal lectins has been the source of intense recent investigations. Isothermal titration microcalorimetry (ITC) provides direct determination of the thermodynamics of binding of carbohydrates to lectins, and has provided important insights into the fine carbohydrate binding specificities of a wide number of plant and animal lectins. Recent ITC studies have been performed with galectin-1, galectin-3 and galectin-7 and their interactions with sialylated and non-sialylated carbohydrates. The results show important differences in the specificities of these three galectins toward poly-N-acetyllactosamine epitopes found on the surface of cells.
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PMID:Thermodynamic binding studies of galectin-1, -3 and -7. 1475 69

Nuclear extracts (NE), capable of carrying out splicing of pre-mRNA, contain galectin-1 and galectin-3. NE depleted of galectins-1 and -3 concomitantly lose their splicing activity. The activity of the galectin-depleted extract can be reconstituted by the addition of either galectin-1 or galectin-3. These results suggest that galectins-1 and -3 serve as redundant splicing factors. Consistent with this notion, immunofluorescence staining showed that both galectins yielded a diffuse nucleoplasmic distribution, matching that of nascent transcripts and consistent with the hypothesis that bulk transcription and pre-mRNA processing occur throughout the nucleoplasm. Under some conditions, the galectins could be found in speckled structures and nuclear bodies but the prevailing thought is that these represent sites of storage and recycling rather than sites of action. Galectin-1 and galectin-3 bind directly to Gemin4, a component of the SMN core complex, which plays multiple roles in ribonucleoprotein assembly, including the biogenesis, delivery, and recycling of snRNPs to the spliceosome. Thus, galectin-1 and galectin-3 constitute a part of an interacting dynamic network of many factors involved in the splicing and transport of mRNA.
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PMID:Understanding the biochemical activities of galectin-1 and galectin-3 in the nucleus. 1475 73

Members of the galectin family are presently known to participate in cellular homeostasis by modulating cell growth, controlling cell cycle progression, and inducing or inhibiting apoptosis. Both intracellular and extracellular activities of galectins have been described, with the former typically independent of lectin activity, and the latter mediated by lectin activity. Galectin-1 and -3 are recognized as activators and inducers of cell stasis in extracellular capacities. Galectin-1, -7, -8, -9 and -12 are characterized as promoters or inducers of apoptosis, while galectin-3 is demonstrated as an inhibitor of apoptosis intracellularly. Localization studies of galectins have established that these proteins can segregate into multiple intracellular compartments, and the preference for segregation is dependent on the status of the cell. Localization would, therefore, likely correspond to compartmental function. While galectin-1 and -3 have been the most abundantly expressed and extensively studied, and therefore, the members best understood, expanding interest in galectins has resulted in description of new members that display more restricted expression patterns, suggesting more specific activity. Nevertheless, as demonstrated for many members, it appears that a major feature of the galectin family is the homeostatic regulation of cells.
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PMID:Regulation of cellular homeostasis by galectins. 1475 74

A large body of literature has examined and described galectin expression in cancer. Discrepancies have been observed in the reported data, which hampered clear understanding of the expression profiles. This relates to the use of different types of methods that evaluate either global or specific gene expression in heterogeneous cancer tissue samples, type of antibodies used in immunohistochemistry and procedures of comparison of gene expression. In this manuscript, we review the main data concerning expression of galectins in human cancer. Only galectin-1 and galectin-3, the most abundant and examined galectins, will be examined here.
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PMID:Expression of galectins in cancer: a critical review. 1475 77

Galectins and their ligands have been implicated in cell transformation and cancer metastasis, and found to have prognostic value. Mac-2 BP, also known as 90K, is a highly glycosylated, secreted protein extensively studied in human cancer, which binds galectin-1, galectin-3 and galectin-7. High expression levels of 90K are associated with a shorter survival, the occurrence of metastasis or a reduced response to chemotherapy in patients with different types of malignancy. The mechanisms underlying the prognostic significance of 90K and galectins in cancer are far from being understood, although they may be related to the ability of these proteins to interact and, to some extent, modulate cell-cell and cell-matrix adhesion and apoptosis. The resulting scenario is even more complex, as data have been presented that all these proteins might be associated with either a positive or a negative outcome of the patients. It is hypothesised that different galectins and galectin ligands with overlapping or opposite functions, expressed in different tumors during the different steps of the metastatic cascade might play a crucial role in tumor progression.
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PMID:90K (Mac-2 BP) and galectins in tumor progression and metastasis. 1475 79


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