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Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pigmented human melanoma cell line, MM418, became demelanized when treated continuously with a nontoxic level of halistanol trisulphate (HTS), a C29 steroidal detergent isolated from a marine sponge. Nontoxic levels of halistanol or of a range of anionic, cationic and neutral detergents had no such effect. Control MM418 cells varied greatly in size, appearance and pigmentation; HTS-treated cells were smaller than controls, had a uniform, generally bipolar appearance, and lacked pigment. HTS induced only minor changes in cell ultrastructure, with fewer mature melanosomes being found in treated cells. Suppression of melanin synthesis was apparent within 24 h of addition of HTS, as judged by inhibited incorporation of the false precursor, 5[125I]-2-thiouracil. Reversal of inhibition occurred within the same period after removal of HTS. Tyrosinase activity gradually decreased to 25% of the control value during a 19-day treatment with HTS, and expression of two carbohydrate-dependent tyrosinase epitopes, 5C12 and 2B7, was abolished. Expression of one other melanosomal protein and of vimentin was not affected. The results suggest that HTS inhibits maturation of tyrosinase to a form associated with melanin synthesis.
Melanoma Res
PMID:Reversible depigmentation of human melanoma cells by halistanol trisulphate, a novel marine sterol. 138 55

Genetic studies have implicated the early involvement of a gene on chromosome arm 9p in the development of cutaneous melanoma. We have performed loss-of-heterozygosity studies to confirm these original findings and identify the most frequently rearranged or deleted region of 9p. Eight markers were analyzed, including (from 9pter to proximal 9q) D9S33, the beta-interferon (IFNB1) locus, the alpha-interferon (IFNA) gene cluster, D9S126, D9S3, D9S19, the glycoprotein 4 beta-galactosyltransferase (GGTB2) gene, and the argininosuccinate synthetase pseudogene 3 (ASSP3). Two or more of these loci were found to be hemizygously reduced in 12 of 14 (86%) informative metastatic melanoma tumor and cell line DNAs, and homozygous deletions of the marker D9S126 were observed in 2 of 20 (10%) melanoma cell lines. These findings have resulted in the identification of a small critical region of 2-3 megabases on 9p21 in which a putative melanoma tumor-suppressor gene appears likely to reside. Several 9p candidate genes, including IFNB1, the IFNA gene cluster, GGTB2, and the tyrosinase-related protein (TYRP) locus, have all been eliminated as potential targets because they are located outside of the homozygously deleted regions.
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PMID:Homozygous deletions within human chromosome band 9p21 in melanoma. 143 46

We have cloned and sequenced the human genomic DNA segments encoding the 5'-flanking region and the first two exons of the tyrosinase-related protein (TRP) gene, a pigment cell-specific gene. Functional analysis of its promoter suggests that the downstream region of the TRP gene, including the first intron, enhances the transient expression of the luciferase gene under control of the TRP gene promoter about 16- to 20-fold. This enhancer-like activity is detected not only in melanoma cells but also in HeLa cells whose TRP gene expression is assumed to be repressed. We suggest a possibility that the downstream region is not sufficient to confer pigment cell-specific expression, but is required for efficient transcription of the TRP gene in pigment cells.
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PMID:Downstream region of the human tyrosinase-related protein gene enhances its promoter activity. 157 33

The TYRP (brown) locus determines pigmentation and coat color in the mouse. The human homolog of the TYRP locus has been recently identified and shown to encode a 75-kDa transmembrane melanosomal glycoprotein called gp75. The gp75 glycoprotein is homologous to tyrosinase, an enzyme involved in the synthesis of melanin, forming a family of tyrosinase-related proteins. A genomic clone of human gp75 was used to map the human TYRP locus to chromosome 9, region 9p23, by nonradioactive fluorescent in situ hybridization. Specificity of hybridization was tested with a genomic fragment of human tyrosinase that mapped to a distinct site on 11q21. The 9p region has been reported to be nonrandomly altered in human melanoma, suggesting a role for the region near the TYRP locus in melanocyte transformation.
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PMID:Assignment of the human TYRP (brown) locus to chromosome region 9p23 by nonradioactive in situ hybridization. 157 87

Only a few autoantigenic human tumor antigens have been purified and characterized. We employed the monoclonal antibody (MAb) TA99 to isolate, purify and partially characterize an autoantigenic intracellular glycoprotein, gp75, from human melanoma cells. The gp75 antigen is the most abundant glycoprotein expressed in human melanocytes and pigmented melanomas and is the human homologue of the mouse brown locus gene product. Differential solubilization of melanoma membrane fraction and subcellular fractionation of pigmented melanoma cells showed that gp75 is an integral membrane protein localized to melanosomes. The gp75 glycoprotein eluted as a broad peak during ion exchange chromatography and appeared as a protein with broad pI (pI 5.5-5.9), consistent with charge microheterogeneity. gp75 also exhibited heterogeneity of binding to concanavalin A. Tyrosine hydroxylase (tyrosinase) activity co-purified with gp75 during membrane solubilization and anion exchange and Con A chromatography. However, most tyrosine hydroxylase activity could be dissociated from gp75 antigen during MAb TA99 affinity chromatography. TA99 did not immunoprecipitate or deplete tyrosine hydroxylase activity from lysates of human melanoma cells. Attempts to obtain N-terminal amino acid sequence of purified gp75 were not successful due to blocked N-terminus. Amino acid composition of gp75 was similar to that of tyrosinase. Physicochemical similarities and limited identity in the primary structure between gp75 and tyrosinase support the conclusion that the gp75 antigen does not exhibit tyrosine hydroxylase activity, but is a member of a tyrosinase-related family of proteins.
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PMID:Purification of an autoantigenic 75-kDa human melanosomal glycoprotein. 167 Oct 31

The mouse brown locus encodes a tyrosinase-related protein, TRP-1. The human homolog of TRP-1 was recently cloned from a melanoma cDNA library and sequenced. We have made oligonucleotide primers corresponding to the human TRP1 3' untranslated region and used them to map the human TRP1 gene by species-specific PCR in human/rodent somatic cell hybrids. By this means, the human TRP1 gene has been mapped to the short arm of chromosome 9.
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PMID:The human homolog of the mouse brown gene maps to the short arm of chromosome 9 and extends the known region of homology with mouse chromosome 4. 176 62

Two groups of cDNA clones were isolated by screening a lambda gt11 cDNA library of normal human melanocytes with antityrosinase antibodies: one group of 13 was related to the human tyrosinase gene. The properties of the other group of three cDNA clones was investigated by the use of a representative clone, Pmel 17-1. The cDNA hybridized to an mRNA species of approximately 2600 bases from human and murine melanocytes. The transcript of Pmel 17-1 (17-1 mRNA) was expressed preferentially in melanocytes and its abundance paralleled the melanin content. The expression of Pmel 17-1 mRNA increased after stimulation of human and murine melanoma cells with agents that increase the levels of melanization. Immunocompetition assays with monoclonal antibodies to gp75, a known pigmentation-associated antigen of melanocytes, suggested that Pmel 17-1 encodes a 75,000 Mr glycoprotein that is highly abundant in melanotic cells and shares some immunological homology with tyrosinase. The gene for Pmel 17-1 did not map at or near the c-albino locus in mice. The cDNA of Pmel 17-1 detected a single hybridizing restriction fragment in both human and murine DNA, indicating that the gene has been conserved between these two species and exists as a single gene in each.
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PMID:A melanocyte-specific complementary DNA clone whose expression is inducible by melanotropin and isobutylmethyl xanthine. 244 95

The toxicity and selectivity of 3,4-dihydroxybenzylamine (DHBA), an experimental antimelanoma agent that cannot enter the melanin pathway, broadly paralleled that of L-dopa in a panel of human melanoma cell lines sensitive or resistant to the latter drug. A human retinoblastoma cell line was found to be sensitive to both compounds. The toxicity and selectivity of both catechols were associated with inhibition of DNA synthesis; DHBA was more potent yet allowed a much greater degree of recovery compared with an equitoxic level of dopa. Dopa and DHBA had similar, dose-dependent effects on the cell cycle, arresting cells in S phase at low doses and in G1 at high doses. Replication of the DNA virus adenovirus was found to be inhibited by both agents. There was no difference between sensitive and resistant cell lines in the manganese or copper/zinc forms of superoxide dismutase, or in iron content and iron-binding capacity. Catechol toxicity was inhibited by the hydrogen peroxide scavenging agents pyruvate and methaemoglobin. Sensitivity to catechols did not correlate with melanin or tyrosinase content, rate of incorporation of tyrosine or dopa, intracellular levels of phenylalanine or tyrosine, or binding of a new monoclonal antibody directed against a melanosomal protein. These results indicate that DHBA and dopa exhibit selective toxicity for neural crest tumor cells independently of the melanisation pathway and of the superoxide scavenging system.
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PMID:Melanin synthesis and the action of L-dopa and 3,4-dihydroxybenzylamine in human melanoma cells. 290 84

The positive reactivity and specificity of a mouse monoclonal antibody (MoAb) human melanosome-specific antigen (HMSA) 2 raised against the melanosomal protein with amelanotic malignant melanoma on routine paraffin sections is reported. MoAb HMSA-2 identified cytoplasmic antigen with the following specifications: (1) a sharp heterogeneous expression in melanoma cells (acral lentiginous melanoma [ALM], 11 of 14; superficial spreading melanoma [SSM], 13 of 14; nodular melanoma [NM], one of three; and lentigo maligna melanoma [LMM], zero of two), whereas a diffuse homogeneous expression in cells of benign pigmented melanocytic nevi; and (2) an intense expression on amelanotic melanoma cells as opposed to a weak or negative expression on highly melanotic cells. The positive reactivity of MoAb HMSA-2 with amelanotic melanomas was exemplified by two shave-biopsy specimens of amelanotic subungual and plantar lesions, and by two cases of axillary and cervical amelanotic nodes that were left undiagnosed on routine hematoxylin and eosin (H & E) sections because of lack of melanin pigments. These were found, after diagnosis with MoAb HMSA-2, to possess the regressed primary lesions (both ALM).
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PMID:Specification and use of a mouse monoclonal antibody raised against melanosomes for the histopathologic diagnosis of amelanotic malignant melanoma. 304 72

A mouse melanoma cDNA clone was isolated by virtue of its reactivity with two antisera raised against tyrosinase (EC 1.14.18.1) from two species, hamster and mouse. The cDNA (5A) cross-hybridizes with another, pMT4 [Shibahara, S., Tomita, V., Sakakura, T., Nager, C., Bhabatosh, C. & Muller, R. (1986) Nucleic Acids Res. 14, 2413-2427], previously thought to encode mouse tyrosinase. Two other cDNAs, one human and one mouse, have been reported recently [Kwon, B. S., Haq, A. K., Pomerantz, S. H. & Halaban, R. (1987) Proc. Natl. Acad. Sci. USA 84, 7473-7477; and Yamamoto, H., Takeuchi, S., Kudo, T., Makino, K., Nakata, A., Shinoda, T. & Takeuchi, T. (1987) Jpn. J. Genet. 62, 271-277] as candidates for tyrosinase, and they map at or very close to the mouse albino (c) locus. The proteins they encode are very similar to each other but are distinct from (although related to) the pMT4-encoded protein. Here I use recombinant inbred strains to localize pMT4 at or close to the mouse brown (b) locus. I suggest that the gene mapping to c is the authentic tyrosinase gene, whereas that mapping to b encodes a tyrosinase-related protein. All b mutations in laboratory strains are associated with the same diagnostic Taq I fragment, suggesting that all derive from the same original mutation. I discuss possible function(s) of the tyrosinase-related protein.
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PMID:A cDNA encoding tyrosinase-related protein maps to the brown locus in mouse. 313 13


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