Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

G protein-coupled receptor 30 (GPR30), a seven-transmembrane receptor (7TMR), is associated with rapid estrogen-dependent, G protein signaling and specific estrogen binding. At present, the subcellular site of GPR30 action is unclear. Previous studies using antibodies and fluorochrome-labeled estradiol (E2) have failed to detect GPR30 on the cell surface, suggesting that GPR30 may function uniquely among 7TMRs as an intracellular receptor. Here, we show that detectable expression of GPR30 on the surface of transfected HEK-293 cells can be selected by fluorescence-activated cell sorting. Expression of GPR30 on the cell surface was confirmed by confocal microscopy using the lectin concanavalin A as a plasma membrane marker. Stimulation of GPR30-expressing HEK-293 cells with 17beta-E2 caused sequestration of GPR30 from the cell surface and resulted in its codistribution with clathrin and mobilization of intracellular calcium stores. Evidence that GPR30 signals from the cell surface was obtained from experiments demonstrating that the cell-impermeable E2-protein conjugates E2-BSA and E2-horseradish peroxidase promote GPR30-dependent elevation of intracellular cAMP concentrations. Subcellular fractionation studies further support the plasma membrane as a site of GPR30 action with specific [3H]17beta-E2 binding and G protein activation associated with plasma membrane but not microsomal, or other fractions, prepared from HEK-293 or SKBR3 breast cancer cells. These results suggest that GPR30, like other 7TMRs, functions as a plasma membrane receptor.
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PMID:Activation of the novel estrogen receptor G protein-coupled receptor 30 (GPR30) at the plasma membrane. 1737 46

In this study, lectin binding was compared with pathological prognostic factors and clinical follow-up details. Formalin-fixed, paraffin-embedded tissues from 43 cases of breast carcinoma were studied for binding with Ulex Europeus Agglutinin (UEA-I) lectin. Staining results were compared with tumor size, histologic and nuclear grade, lymph node status (number, capsular and pericapsular invasion), blood and lymphatic vessel invasion, ER and PR status, clinical stage and the patients' short-term follow-up details. Analysis of staining with UEA-I showed a significant relationship with blood vessel invasion (P < 0.01) and lymphatic vessel invasion (P < 0.05). Furthermore, PR showed a significant inverse correlation with lectin binding (P < 0.05). Staining with UEA-I related significantly with axilliary lymph node metastases (P < 0.05). UEA-I was positive in four (66.6%) out of six cases with distant organ mestastasis. This study confirms that, in breast cancer, lectin binding to the cancer cells can be a reliable indicator for axilliary metastases, and the need for additional therapeutic interventions.
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PMID:Ulex Europeus Agglutinin (UEA-I) lectin binding in breast carcinoma and its relationship to prognostic factors. 1742 27

Helix pomatia agglutinin (HPA) is a lectin that has been used extensively in histopathology, since its binding to tissue sections from breast and colon cancers is correlated with the worst prognosis for the patients. The lectin recognizes alpha-d-N-acetylgalactosamine (alphaGalNAc) containing epitopes which are only present in cancer cell lines having a high likelihood to undergo metastasis, such as the HT29 cancer colon cell line. Several breast cancer cell lines have also been shown to be labeled, although IGROV1, an ovarian cancer cell line, is not. Inhibition studies, using GalNAc monosaccharides, are reported here, showing that the labeling is dependent upon the presence of carbohydrate epitopes. The crystal structures of the lectin complexed with two GalNAc containing epitopes associated with cancer, the Tn (alphaGalNAc-Ser) and Forssman (alphaGalNAc1-3GalNAc) antigens, show the lectin's specificity for GalNAc is due to a particular network of hydrogen bonds. A histidine residue makes hydrophobic contact with the aglycon, rationalizing the preference for GalNAc bearing an additional sugar or amino acid in the alpha position. These structures provide the molecular basis for the use of HPA in metastasis research.
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PMID:Structural basis for recognition of breast and colon cancer epitopes Tn antigen and Forssman disaccharide by Helix pomatia lectin. 1765 9

Adhesion of cancer cell to endothelial cells and the subsequent trans-endothelial migration are key steps in metastasis. However, the identities of the molecules mediating cancer cell/endothelial cell interaction are still not fully understood. In this study, we tested the hypothesis that lectin-like oxidized-low-density lipoprotein (oxLDL) receptor-1 (LOX-1), a key mediator of vascular inflammation and atherosclerosis expressed on endothelial cell surface, mediates breast cancer cell/endothelial cell interactions. We showed that up-regulation of endothelial LOX-1 by TNF-alpha promoted the adhesion and trans-endothelial migration of MDA-MB-231 breast cancer cells. Thus, endothelial LOX-1 could present a novel pathway in breast cancer metastasis.
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PMID:Up-regulation of LOX-1 expression by TNF-alpha promotes trans-endothelial migration of MDA-MB-231 breast cancer cells. 1786 83

Breast cancer is the most common cancer among women. Androgens, the male sexual hormones produced by ovary, act as protector of mammary gland. To elucidate the possible effects of dihydrotestosterone (DHT) on the transcriptome of mammary gland, serial analysis of gene expression was carried out on three groups of gonadectomized mice. After gonadectomy (GDX), DHT was injected 3 or 24h before sacrifice, whereas the control (GDX) group received vehicle solution. Approximately 42,000 tags were sequenced in each group. Genes involved in the cytoskeletal and extracellular matrix, such as troponin I skeletal fast 2 and keratin complex 1 acidic gene 14, were upregulated. In the immunity, complement component 1 q subcomponent gamma polypeptide and expressed sequence tag similar to lectin galactose binding soluble 3 were downregulated by DHT, whereas serine (or cystein) proteinase inhibitor clade A member 1a was upregulated. In the energy metabolism, the gene expression level of cytochrome c oxidase subunit I was upregulated by DHT, while NADH dehydrogenase subunit 2 was downregulated. In addition, transcripts involved in transport metabolism, such as apolipoprotein A-1, were upregulated by DHT, whereas retinol binding protein 4 plasma was downregulated. Several previously unknown sequence tags were identified, which may allow to characterize new molecules of interest. These results suggest the suppression of immune response in normal mammary gland after DHT injection. This study can assist in refining research on the role of androgens in mammary gland homeostasis and breast cancer.
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PMID:Effects of dihydrotestosterone on gene expression in mammary gland. 1860 97

Protein glycosylation is a common post-translational modification that is involved in many biological processes, including cell adhesion, protein-protein and receptor-ligand interactions. The glycoproteome constitutes a source for identification of disease biomarkers since altered protein glycosylation profiles are associated with certain human ailments. Glycoprotein analysis by mass spectrometry of biological samples, such as blood serum, is hampered by sample complexity and the low concentration of the potentially informative glycopeptides and -proteins. We assessed the utility of lectin-based and HILIC-based affinity enrichment techniques, alone or in combination, for preparation of glycoproteins and glycopeptides for subsequent analysis by MALDI and ESI mass spectrometry. The methods were successfully applied to human serum samples and a total of 86 N-glycosylation sites in 45 proteins were identified using a mixture of three immobilized lectins for consecutive glycoprotein enrichment and glycopeptide enrichment. The combination of lectin affinity enrichment of glycoproteins and subsequent HILIC enrichment of tryptic glycopeptides identified 81 N-glycosylation sites in 44 proteins. A total of 63 glycosylation sites in 38 proteins were identified by both methods, demonstrating distinct differences and complementarity. Serial application of custom-made microcolumns of mixed, immobilized lectins proved efficient for recovery and analysis of glycopeptides from serum samples of breast cancer patients and healthy individuals to assess glycosylation site frequencies.
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PMID:Assessment of lectin and HILIC based enrichment protocols for characterization of serum glycoproteins by mass spectrometry. 1863 81

The membrane glycoprotein component of the cellular proteome represents a promising source for potential disease biomarkers and therapeutic targets. Here we describe the development of a method that facilitates the analysis of membrane glycoproteins and apply it to the differential analysis of breast tumor cells with distinct malignant phenotypes. The approach combines two membrane extraction procedures, and enrichment using ConA and WGA lectin affinity columns, prior to digestion and analysis by LC-MS/MS. The glycoproteins are identified and quantified by spectral counting. Although the distribution of glycoprotein expression as a function of MW and p I was very similar between the two related cell lines tested, the approach enabled the identification of several distinct membrane glycoproteins with an expression index correlated with either a precancerous (MCF10AT1), or a malignant, metastatic cellular phenotype (MCF10CA1a). Among the proteins associated with the malignant phenotype, Gamma-glutamyl hydrolase, CD44, Galectin-3-binding protein, and Syndecan-1 protein have been reported as potential biomarkers of breast cancer.
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PMID:Membrane glycoproteins associated with breast tumor cell progression identified by a lectin affinity approach. 1872 97

A dimeric 62-kDa lectin exhibiting a novel N-terminal amino acid sequence was purified from caper (Capparis spinosa) seeds. The purification protocol involved anion-exchange chromatography, cation-exchange chromatography and, finally, gel filtration by FPLC on Superdex 75. Approx. 100-fold purification was achieved. The haemagglutinating activity of the lectin, which was stable in the pH range 1-12 and up to 40 degrees C, could be inhibited by D(+) galactose, alpha-lactose, raffinose and rhamnose at 1 mM concentration, by 25 mM L(+)-arabinose and by 100 mM D(+)GlcN (glucosamine). The lectin potently inhibited HIV-1 reverse transcriptase with an IC50 of 0.28 microM and proliferation of both hepatoma HepG2 and breast cancer MCF-7 cells with an IC50 of approx. 2 microM. It induced apoptosis in HepG2 and MCF-7 cells. It manifested a weaker mitogenic activity on mouse splenocytes than ConA (concanavalin A). It inhibited mycelial growth in Valsa mali with an IC50 of 18 microM.
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PMID:Isolation and characterization of a lectin with potentially exploitable activities from caper (Capparis spinosa) seeds. 1884 34

A dimeric 64-kDa melibiose-binding lectin was isolated from the seeds of Bauhinia variegata. The isolation procedure comprised affinity chromatography on Affi-gel blue gel, ion exchange chromatography on Mono Q, and gel filtration on Superdex 75. The lectin was adsorbed on the first two chromatographic media. Its hemagglutinating activity was stable after 30-min exposure to temperatures up to 70 degrees C. Since lectins may demonstrate biological activities such as antiproliferative, immunomodulatory, antifungal, antiviral, and HIV-1 reverse transcriptase inhibitory activities, the isolated lectin was tested for these activities. It was found that the lectin inhibited proliferation in hepatoma HepG2 cells and breast cancer MCF7 cells with an IC(50) of 1.4 microM and 0.18 microM, respectively. HIV-1 reverse transcriptase activity was inhibited with an IC(50) of 1.02 microM. The lectin and concanavalin A (Con A) evoked maximal mitogenic response from mouse splenocytes at similar concentrations, but the maximal response to B. variegata lectin was only 1/5 of that induced by Con A in magnitude. B. variegata lectin was devoid of antifungal activity.
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PMID:Preparation and biological properties of a melibiose binding lectin from Bauhinia variegata seeds. 1894 41

Aberrant glycosylation occurs in essentially all types of human cancers. A difference in glycopattern of proteins will result in a change of function of the proteins. The lectin from Helix pomatia (HPA) recognizes N-acetylgalactosaminylated glycoproteins and very consistent results over the increased binding of HPA in tissue sections are associated with metastasis progression and poor patient prognosis in a range of human adenocarcinomas. The induced modification of protein function after changed glycosylation is unknown, and as a part in characterizing the glycoproteins carrying the specific carbohydrates, we analyzed the major HPA binding proteins in sera from healthy women, women with primary breast cancer with no metastasis (bcmet-), and women with metastasizing breast cancer (bcmet+) using lectin affinity chromatography and lectin blotting. The binding ligands were further identified using mass spectrometry (MALDI-TOF MS) to confirm the captured glycoproteins. The major HPA binding proteins in serum were found to be IgA1, complement factor C3, von Willebrand factor (vWF), alpha-2-macroglobulin and IgM. This set of antigens is a panel of candidates for useful HPA related biomarkers in sera, but our results also emphasize the fact that the blood group phenotypes are of most importance when using the lectin HPA in recognition of cancer biomarkers in sera and plasma. The results emphasize that interpretation of an individual change in the glycosylation pattern of a specific tumor marker always needs to be analyzed in its right context. This study shows that the blood group phenotypes can have a major impact on the results when analyzing HPA lectin binding.
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PMID:Expression of Helix pomatia lectin binding glycoproteins in women with breast cancer in relationship to their blood group phenotypes. 1899 22


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