Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Synthesis of the biotinylated T-antigens, linked to a serine by an alpha (7 alpha) or a beta (7 beta) 2-acetamido-2-deoxy-D-galactoside bond, is described. These derivatives were needed for the detection of a specific endogenous lectin at the surface and/or on the migration pathway of melanoma cells. In the course of the synthesis, an unusual lactam formation was observed with the beta anomer of the azido-disaccharide 5 beta.
 ...
PMID:Unusual lactam formation occurring in the synthesis of a biotinylated T-antigen-serine derivative. 934 50

To survive in a mechanically active environment, cells must adapt to variations of applied membrane tension. A collagen-coated magnetic bead model was used to apply forces directly to the actin cytoskeleton through integrin receptors. We demonstrate here that by a calcium-dependent mechanism, human fibroblasts reinforce locally their connection with extracellular adhesion sites by inducing actin assembly and by recruiting actin-binding protein 280 (ABP-280) into cortical adhesion complexes. ABP-280 was phosphorylated on serine residues as a result of force application. This phosphorylation and the force-induced actin reorganization were largely abrogated by inhibitors of protein kinase C. In a human melanoma cell line that does not express ABP-280, actin accumulation could not be induced by force, whereas in stable transfectants expressing ABP-280, force-induced actin accumulation was similar to human fibroblasts. Cortical actin assembly played a role in regulating the activity of stretch-activated, calcium-permeable channels (SAC) since sustained force application desensitized SAC to subsequent force applications, and the decrease in stretch sensitivity was reversed after treatment with cytochalasin D. ABP-280-deficient cells showed a > 90% increase in cell death compared with ABP-280 +ve cells after force application. We conclude that ABP-280 plays an important role in mechanoprotection by reinforcing the membrane cortex and desensitizing SACs.
 ...
PMID:The role of actin-binding protein 280 in integrin-dependent mechanoprotection. 943 Jul 14

Germline mutations at loci encoding the transcription factor Microphthalmia (Mi), the cytokine receptor c-Kit, or its ligand Steel factor (S1) result in strikingly similar defects in mast cell and melanocyte development. Here we describe a biochemical link between Kit signalling and the activity of Mi. Stimulation of melanoma cells with S1 results in activation of MAP kinase, which in turn phosphorylates Mi at a consensus target serine. This phosphorylation upregulates Mi transactivation of the tyrosinase pigmentation gene promoter. In addition to modulating pigment production, such signalling may regulate the expression of genes essential for melanocyte survival and development. The pathway represents a new application of the general MAP kinase machinery in transducing a signal between a tissue-specific receptor at the cell surface and a tissue-specific transcription factor in the nucleus.
 ...
PMID:MAP kinase links the transcription factor Microphthalmia to c-Kit signalling in melanocytes. 944 Jun 96

To identify shared epitopes for melanoma-reactive CTL restricted by MHC molecules other than HLA-A*0201, six human melanoma patient CTL lines expressing HLA-A1 were screened for reactivity against the melanocyte differentiation proteins Pmel-17/gp100, MART-1/Melan-A, and tyrosinase, expressed via recombinant vaccinia virus vectors. CTL from five of the six patients recognized epitopes from tyrosinase, and recognition of HLA-A1+ target cells was strongly correlated with tyrosinase expression. Restriction by HLA-A1 was further demonstrated for two of those tyrosinase-reactive CTL lines. Screening of 119 synthetic tyrosinase peptides with the HLA-A1 binding motif demonstrated that nonamer, decamer, and dodecamer peptides containing the sequence KCDICTDEY (residues 243-251) all reconstituted the CTL epitope in vitro. Epitope reconstitution in vitro required high concentrations of these peptides, which was hypothesized to be a result of spontaneous modification of cysteine residues, interfering with MHC binding. Substitution of serine or alanine for the more N-terminal cysteine prevented modification at that residue and permitted target cell sensitization at peptide concentrations 2 to 3 orders of magnitude lower than that required for the wild-type peptide. Because spontaneous modification of sulfhydryl groups may also occur in vivo, tumor vaccines using this or other cysteine-containing peptides may be improved by amino acid substitutions at cysteine residues.
 ...
PMID:Human melanoma patients recognize an HLA-A1-restricted CTL epitope from tyrosinase containing two cysteine residues: implications for tumor vaccine development. 949 46

The nm23 genes were discovered on the basis of their reduced expression by highly metastatic cell lines. This trend was confirmed in cohorts of several types of human carcinomas and melanomas. Several transfection studies have demonstrated the suppressive effect of nm23 overexpression on the metastatic aggressiveness of melanoma and breast carcinoma cells in vivo. These transfection experiments have also demonstrated an effect of nm23 overexpression on cellular functions involved in the metastatic phenotype, such as cell motility, and point to a regulatory role for Nm23 proteins in cellular signalling pathways. Nm23 homologues from various species are also involved in normal tissue development and differentiation. Transfection of nm23-H1 into breast cancer cells provided a functional demonstration of the involvement of this gene in the differentiation of mammary epithelial cells. However, the molecular mechanism of these biological effects remains unknown. Several biochemical activities have been reported for Nm23, including NDP kinase activity, serine autophosphorylation and protein-histidine kinase activity. To define the possible significance of these biochemical activities, we carried out site-directed mutagenesis of the relevant codons of nm23-H1 cDNA and studied the effects upon transfection into MDA-MB-435 human breast carcinoma cells. We have also used Nm23 expression as a molecular marker to identify novel compounds that are active against the most aggressive tumour cells. This approach revealed that none of the standard agents currently in clinical use is preferentially active against the most aggressive tumour cells, and allowed us to identify new compounds that are preferentially inhibitory towards low-Nm23-expressing breast carcinoma and melanoma cell lines. This analysis also revealed a significant correlation between Nm23 levels and sensitivity of the tumour cells to alkylating agents. A functional implication of Nm23 proteins in this phenomenon was demonstrated after transfection of nm23 cDNAs into melanoma and breast and ovarian carcinoma cells.
 ...
PMID:Nm23 and tumour metastasis: basic and translational advances. 951 29

The cell undergoes a diverse range of stimulations including growth factor activation and signal transduction from adhesion receptors, such as cadherins. In the absence of a mitogenic signal from outside the cell, beta catenin is sequestered in complexes with the product of the adenomatous polyposis coli (APC) gene and a serine threonine glycogen kinase (GSK 3 beta) enabling degradation of free beta catenin. Residual catenins hold cells together by binding to cadherins both at adherens junctions and the actin cytoskeleton. When a mitotic signal is delivered by the wnt pathway, GSK 3 beta is antagonised so that beta catenin can no longer be degraded. Cytosolic concentrations rise and binding to other newly synthesised proteins occurs, especially transcription factors that are transported to the nucleus, such as lymphocyte enhancing factor and T cell factor. This article discusses the signalling between mitogenic and adhesion pathways and suggests that it is a global mechanism for development, differentiation, and disease. These changes in catenin and APC biology may not be sufficient alone to transform cells fully but they appear to be a necessary final common pathway for several cancers of the mucous secreting crypts (including Barrett's oesophageal lesions and colorectal cancer) or stratified secreting epithelium (melanoma) before invasion.
 ...
PMID:Cadherin and catenin biology represent a global mechanism for epithelial cancer progression. 953 77

The increased cell surface expression of the serine integral membrane protease, seprase, has been associated with the invasive behavior of human melanoma cell lines in vitro. The present study investigates the expression of seprase in malignant, premalignant, benign, and normal human breast tissues. The 170-kDa gelatinase activity of seprase was identified in extracts of infiltrating ductal carcinomas (IDC). Protein bands corresponding to the proteolytically active 170-kDa seprase dimer and its 97-kDa seprase subunit protein were identified by immunoblot analysis of IDC extracts using an antiserum elicited against immunoaffinity-purified seprase. Immunohistochemical analysis of seprase expression in 41 formalin-fixed and paraffin-embedded specimens of human breast tissue revealed preferential immunoreactivity with the malignant cells of IDC (27 cases). Within individual IDC specimens, the stromal cells or morphologically normal epithelium revealed low labeling that was always significantly less than the labeling of neoplastic cells. Lymph node metastases of IDC cells were also strongly positive, but the lymphoid tissue in affected nodes was not stained. Neoplastic cells in DC in situ (5 cases) exhibited variable levels of staining. Epithelial cells of benign fibroadenoma specimens (2 cases) and benign proliferative breast disease (5 cases) exhibited little or no immunoreactivity. Epithelial cells of normal breast tissue (1 case) were not stained. The overexpression of seprase by DC cells is consistent with seprase having a role in facilitating invasion and metastasis of IDC of the breast. The cell surface localization of seprase could be used to target therapeutic agents to malignant breast cells.
 ...
PMID:Seprase, a membrane-bound protease, is overexpressed by invasive ductal carcinoma cells of human breast cancers. 975 65

Blood coagulation and fibrinolysis are activated systemically in patients with malignancy. The precarious balance between coagulation and fibrinolysis is modulated by serine proteinase inhibitors (serpins). Levels of selected serpins (alpha1-antichymotrypsin, alpha1-antitrypsin, alpha2-macroglobulin, antithrombin III, C1 inhibitor, alpha2-antiplasmin), substrates (factor XIIIa, fibrinogen, fibronectin) and endproducts (fibrin/fibrinogen degradation products) of coagulation reactions were measured in the plasma of 61 patients with common malignancies associated with a tendency to thrombosis (i.e. malignant melanoma, gastric cancer and breast cancer). The data revealed a heterogeneity in plasma levels of serpins between tumor types. The most profound differences between cancer and healthy subject groups were found in breast cancer patients. Levels of alpha1-antitrypsin were significantly higher and levels of alpha2-antiplasmin were significantly lower in all cancer groups, whereas there were no differences in antithrombin III levels.
 ...
PMID:Profiles of plasma serpins in patients with advanced malignant melanoma, gastric cancer and breast cancer. 988 64

memA was isolated by subtractive hybridization in which the mRNA repertoire was compared in a panel of human melanoma cell lines with different metastasizing potential. Expression of memA mRNA is elevated in the highly metastasizing human melanoma cell lines and derived xenografts, as compared with the non-metastasizing ones. In a collection of human tumor cell lines and melanoma metastasis lesions, memA mRNA expression could be detected in the A-431 (epidermoid carcinoma), HT-1080 (fibrosarcoma), JEG-3 and JAR (choriocarcinomas) cell lines and in three out of 11 melanoma metastasis lesions. The distribution of memA mRNA in a collection of healthy human organs is also tissue restricted. Sequence analysis revealed that the MEMA protein is identical with a 160 kDa nuclear 'domain rich in serines' (DRS) protein occurring free in the nucleoplasm and in U2-ribonucleoprotein structures. MEMA is also homologous to pinin, a 140 kDa protein associated with the desmosome-intermediate filament complex, and to a 32 kDa porcine neutrophilic protein that was copurified with components of the NADPH-oxidase enzyme complex. The encoded amino acid sequence predicts that the MEMA protein has three coiled-coil domains, one glycine loop domain, is very hydrophilic and contains regions rich in glutamine/proline, glutamic acid and serine residues.
 ...
PMID:memA/DRS, a putative mediator of multiprotein complexes, is overexpressed in the metastasizing human melanoma cell lines BLM and MV3. 1009 61

With the amino acid sequences of all reported Akt kinase physiological substrates, the possible Akt kinase substrate specificity has been suggested. The serine/threonine residue to be phosphorylated in these proteins is placed within stretches of amino acids with homology, and the arginine residues on the -5 and -3 positions and a hydrophobic amino acid on the +2 position are conserved relative to those of serine/threonine residues (XXRXRXXS/TXX). We noticed two putative Akt kinase phosphorylation sites (220GARRRGGSAS229) and (817AVRIRGKSYV826) in human telomerase reverse transcriptase (hTERT) subunit. To demonstrate that hTERT is an Akt kinase substrate protein, we performed the nonradioactive protein kinase assay with the fluorescein hTERT peptide (817AVRIRGKSYV826). We observed the phosphorylation of hTERT peptide by the human melanoma cell lysate or the activated recombinant Akt kinase proteins in vitro. With the treatment of the growth factor deprivation or okadaic acid, we also observed the up-regulation of both hTERT peptide phosphorylation and the telomerase activity. We noticed that Wortmannin down-regulates hTERT peptide phosphorylation and telomerase activity together. In addition, we observed the enhancement of telomerase activity with the pretreatment of Akt kinase in vitro. Thus, these observations suggest that Akt kinase enhances human telomerase activity through phosphorylation of hTERT subunit as one of its substrate proteins.
 ...
PMID:Akt protein kinase enhances human telomerase activity through phosphorylation of telomerase reverse transcriptase subunit. 1022 60


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>