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

A human B lymphoblastoid cell line JWCI-L94 secretes an IgM human monoclonal antibody (HuMAb) that reacts with human melanoma cell lines, M14 and M12. To identify the antigenic epitope of this antibody, we screened lambda gt11 expression libraries constructed from M14 and M12. A total of 12 immunoreactive clones were isolated, and their DNA sequences were determined. The only sequence shared by all these clones was alanine-proline (A-P) at the carboxyl (C) terminal. HuMAb L94 reacted not only with C-terminal A-P-containing fusion proteins, but also with the synthetic dipeptide A-P. None of the peptides containing A-P internally or amino terminally reacted to HuMAb L94. Proline or alanine alone had no ability to bind to HuMAb L94. When alanine was replaced by glycine (G-P) or proline (P-P), the binding activity of these peptides was similar to that of A-P. On the other hand, when alanine was replaced by serine, valine, leucine, glutamine, lysine, methionine, phenylalanine, or hydroxyl proline, the resulting peptide completely lost the antigenic activity of HuMAb L94. These results demonstrate that HuMAb L94 recognizes C-terminal A-P, G-P, or P-P, and that a human antibody can recognize peptides as small as a two-amino acid residue.
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PMID:Peptides with carboxyl-terminal sequence of alanine-proline: detection by a human monoclonal antibody. 753 1

Deficiency of cystathionine beta-synthase (CBS) is a genetic disorder of transsulfuration resulting in elevated plasma homocyst(e)ine and methionine and decreased cysteine. Affected patients have multisystem involvement, which may include light skin and hair. Reversible hypopigmentation in treated homocystinuric patients has been infrequently reported, and the mechanism is undefined. Two CBS-deficient homocystinuric patients manifested darkening of their hypopigmented hair following treatment that decreased plasma homocyst(e)ine. We hypothesized that homocyst(e)ine inhibits tyrosinase, the major pigment enzyme. The activity of tyrosinase extracted from pigmented human melanoma cells (MNT-1) that were grown in the presence of homocysteine was reduced in comparison to that extracted from cells grown without homocysteine. Copper sulfate restored homocyst(e)ine-inhibited tyrosinase activity when added to the culture cell media at a proportion of 1.25 mol of copper sulfate per 1 mol of DL-homocysteine. Holo-tyrosinase activity was inhibited by adding DL-homocysteine to the assay reaction mixture, and the addition of copper sulfate to the reaction mixture prevented this inhibition. Other tested compounds, L-cystine and betaine did not affect tyrosinase activity. Our data suggest that reversible hypopigmentation in homocystinuria is the result of tyrosinase inhibition by homocyst(e)ine and that the probable mechanism of this inhibition is the interaction of homocyst(e)ine with copper at the active site of tyrosinase.
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PMID:Tyrosinase inhibition due to interaction of homocyst(e)ine with copper: the mechanism for reversible hypopigmentation in homocystinuria due to cystathionine beta-synthase deficiency. 761 Dec 81

Adhesion to vascular endothelium is a primary step in the colonization of select target organs by blood-borne cancer cells. Previous studies in our laboratory have shown that adhesion is followed by the establishment of fully functional gap junctional channels between the arrested tumor cell and the endothelium and that gap junctional communication might play an important role in extravasation. Here we report on a critical interdependence between endothelial cell adhesion and communication of lung-metastatic cancer cells. Gap junctions are assembled at focal adhesion contacts between tumor cells and endothelial cells where they mediate metabolic coupling between the junction-forming cell pair. The level of coupling depends on sufficient amounts of connexin43 (cx43) protein expression by both cell partners and, in a rate-limiting fashion, on the expression level of the receptor/ligand pair that mediates adhesion between tumor cells and the endothelium. This conclusion is based on our findings that (a) tumor cells with equal cx43 message, yet different adhesion potential for endothelial cells, differ significantly in their level of communication with the endothelium (e.g., R230AC-MET vs. R3230AC-LR), and (b) gap junctional communication between B16-F10 melanoma cells and lung-matrix-modulated endothelium can be effectively blocked by antiadhesive, anti-Lu-ECAM-1 monoclonal antibody 6D3 and by soluble Lu-ECAM-1. Significantly increased adhesion and communication levels in highly lung-metastatic carcinoma cells imply a role of gap junctional coupling in cancer metastasis, presumably by facilitating extravasation.
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PMID:Adhesion-mediated gap junctional communication between lung-metastatatic cancer cells and endothelium. 765 9

The proto-oncogene c-met product (c-MET) is a receptor tyrosine kinase and functions as a receptor for hepatocyte growth factor (HGF). Although the function of c-MET has yet to be fully clarified, HGF stimulates the phosphorylation of tyrosyl residues on c-MET and triggers the signal transduction pathways, resulting in a contribution to the malignant progression of melanonocytes with synergic factors such as basic fibroblast growth factor and mast cell growth factor. Using immunohistochemical methods, we have studied the localization of c-MET in normal skin and various melanocytic tumours. c-MET was detected in keratinocytes, melanocytes, sebaceous cells, and other cells of the skin. In particular, basal melanocytes almost always showed nuclear labelling. Melanocytic naevi generally revealed predominantly nuclear staining of cells in the epidermis, whereas only a few cases showed a distinct cytoplasmic localization of c-MET in dermal naevus cells. The distribution pattern of c-MET in melanoma cells was basically similar to that of benign lesions, although the numbers tested were small. Cultured human melanoma cells also showed predominantly nuclear labelling, but were unresponsive to exogenous c-MET ligand HGF. Treatment with the glucosidase inhibitor castanospermine caused accumulation of protein at 220 kD, without diminishing the amount of normally-processed 190-kD c-MET. Although there was no significant difference in c-MET distribution between benign and malignant melanocytic lesions, it is suggested that malignant transformation of melanocytes may be associated with loss of response to HGF or other growth-regulating factors.
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PMID:Detection of the c-met proto-oncogene product in normal skin and tumours of melanocytic origin. 782 52

The L and D enantiomers of O-methylmethioninedichloroplatinum(II), chosen for their potential to bind to the GpA sequence of DNA, were prepared and their in vivo activities were measured. Against P388 leukemia both enantiomers showed moderate activity, T/C 128 and 147% for L and D, respectively. Both were inactive against L1210 leukemia and B16 melanoma. The crystal structure of [Pt(O-methyl-L-methionine)Cl2] has been determined by x-ray diffraction methods and refined to a residual of 0.021 for 1299 independent observed reflections. The crystals are monoclinic, space group P2(1); a, 8.698(2); b, 7.124(1); c, 9.198(3) A; beta, 96.71(2) degrees.
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PMID:The preparation and in vivo activity of L- and D-O-methyl-methioninedichloroplatinum(II). The crystal structure of the L-enantiomer. 805 88

The effects of selenium compounds such as sodium selenite, sodium selenate, seleno-DL-cystine and seleno-DL-methionine (100 microM and 10 microM) on B16 and pigmented cloned pB16 murine melanoma cells were investigated in vitro. At the tested concentrations, B16 cells showed a greater sensitivity to the toxic effects of sodium selenite and seleno-DL-cystine than pB16 cells, whereas no decrease of B16 and pB16 cell number was observed after incubation with sodium selenate or seleno-DL-methionine. Glutathione (GSH) percentages were strongly decreased only by selenite and seleno-DL-cystine; it was marked more in B16 than in pB16 cells. The pretreatment of B16 cells with a GSH depleting agent (10 microM buthionine-[S,R]-sulfoximine) did not significantly influence the cytotoxic effects of selenite and seleno-DL-cystine. On both cell populations, GSH preincubation (50 microM) enhanced the cytotoxicity of selenite whereas the survival of seleno-DL-cystine treated cells was increased. Glutathione peroxidase (GSH-Px) activity in B16 cells was more sensitive than in pB16 cells to the activating effect of selenite, and particularly of seleno-DL-cystine: however, cell-free controls indicated that activation was mainly due to glutathione reductase. The rate of 75Se (as sodium selenite) uptake in both cell populations was maximal within the first hour of incubation, with a preferential accumulation in the cytosol; after 24 h of incubation, the amount of 75Se in cytosol and pellet was approximately the same.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of selenium compounds on murine B16 melanoma cells and pigmented cloned pB16 cells. 806 97

The c-MET proto-oncogene encodes the receptor for the Hepatocyte Growth Factor/Scatter Factor, which is known to mediate mitogenic, motogenic and invasive responses of several cell types. We have analysed by immunohistochemistry and biochemically the expression of c-MET in benign and malignant melanocytic lesions. The Met/HGF receptor which in the melanocytic lineage displays the structural features of the authentic receptor was undetectable in tissue melanocytes and in nevocytic nevi. Only four out of 23 primary melanomas scored positive. Expression was increased to a significant level in 17 out of the 44 metastatic lesions examined. The c-MET expression was homogeneous in multiple metastases from the same patients. Comparative analyses showed both lack of correlation with the expression of the tumour progression associated ICAM-1 adhesion molecule and, in 23% of cases, co-expression with the c-KIT encoded receptor. These findings show that the c-MET gene is expressed at late stages of melanoma progression and suggest that the presence of Met/HGF receptor may contribute to the acquisition of an invasive phenotype.
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PMID:Expression of the c-Met/HGF receptor in human melanocytic neoplasms: demonstration of the relationship to malignant melanoma tumour progression. 810 62

HGF-SF stimulates the proliferation of normal human melanocytes in the presence of synergistic factors, one of which is bFGF, and promotes motility and expression of high levels of tyrosinase activity and melanin content. Melanocytes from a recurrent blue nevus were also stimulated by HGF-SF, whereas cells from advanced primary and metastatic lesions either did not respond, were only slightly stimulated or, in one case, were inhibited. Signal transduction was mediated by tyrosyl-phosphorylation of met and several other proteins, including MAP kinase/ERK2. Met expression and phosphorylation in response to HGF-SF was normal in human melanoma cells, and HGF-SF-transduced mouse melanocytes were not tumorigenic. Taken together, the results show that met is not constitutively active in human melanomas and that its activation by an autocrine loop is not sufficient to confer the tumorigenic phenotype. They raise the possibility that exogenous HGF-SF may play a role at early stages of malignant conversion by acting synergistically with bFGF and by promoting the dispersion of factor-dependent cells to ectopic sites.
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PMID:met and HGF-SF in normal melanocytes and melanoma cells. 838 Jul 40

We compared integrin-mediated adhesion to extracellular matrix (ECM) components of cultured human melanocytes and 6 human melanoma cell lines with different metastatic capacities in nude mice. Cultured melanocytes and most melanoma cell lines adhered strongly to fibronectin (FN), whereas only highly metastatic cell lines adhered to laminin (LM), collagen type I (COI) and type IV (COIV). Adhesion to LM and CO could be blocked by anti-alpha 6 and anti-alpha 2 monoclonal antibodies (MAbs) respectively. This observation is consistent with the finding that expression of LM receptor alpha 6 beta 1 and LM/CO receptor alpha 2 beta 1 was low on melanocytes and non- or poorly metastatic cell lines, whereas these integrins were strongly expressed on highly metastatic cell lines. In addition, immunoprecipitation from [35S]-methionine-labeled cells demonstrated increased synthesis of alpha 6, alpha 2 and beta 1 in highly metastatic cell lines and immunohistochemistry showed expression of alpha 6 beta 1 and alpha 2 beta 1 only in xenograft lesions from highly metastatic cell lines. Furthermore, the observation that adhesion of melanocytes and non- or poorly metastatic cell lines could be stimulated with anti beta 1 MAbs demonstrates that these receptors, on these cells, are expressed in an inactive state. Our results suggest that alpha 2 beta 1 and alpha 6 beta 1 play a role in human melanoma metastasis in nude mice and demonstrate that interactions of these integrins with their ligands can be regulated at the level of surface expression and activation state of the receptor.
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PMID:Regulation of integrin-mediated adhesion to laminin and collagen in human melanocytes and in non-metastatic and highly metastatic human melanoma cells. 838 65

We have cloned and characterized multiple messages for cathepsin B that differ in their 5' and 3' untranslated regions (UTRs) from human kidney and the hepatoma cell line HepG2. A comparison of these messages with the cloned human cathepsin B gene reveals that they arise by alternative splicing of a single gene. Processing at a cryptic intron donor site in exon 11 and splicing to exon 12 produces a 4.0-kb message with an alternate 3' UTR in addition to the 2.3-kb message described previously by Chan et al. (1986). Variable removal of exon 2 produces cathepsin B mRNAs which differ by 88 nucleotides in their 5'-UTRs. The ratio of the 2.3-kb to 4.0-kb transcript is about 2:1 in most of the tissues examined, but the ratio of mRNAs with variant 5' UTRs differs widely. Cathepsin B mRNAs lacking exon 2 are predominant in human tumors. In addition, human breast and colon carcinomas and a human melanoma contain a cathepsin B transcript that is also missing exon 3 encoding the signal peptide and 7 residues of the activation propeptide. An in vitro transcription/translation assay was used to demonstrate that this message could be translated from an internal methionine codon (residue 52), producing a 32-kD product lacking the signal peptide and more than half the propeptide. The transcription/translation assay also demonstrated that the variant messages differ in their rates of translation. The relative rates are about 8:2:1 for mRNA lacking exons 2 and 3 compared to mRNA lacking exon 2 and mRNA containing the full-length 5' end, respectively. These results suggest that the expression of cathepsin B in human tissues may be regulated in part at the level of mRNA processing.
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PMID:Characterization of the cathepsin B gene and multiple mRNAs in human tissues: evidence for alternative splicing of cathepsin B pre-mRNA. 849 8


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