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)

Tyrosinase induction in murine malignant melanocytes by alpha MSH is well known, but its molecular basis has not been characterized. Treatment of B16 melanoma cells with theophylline or alpha MSH mediates a larger induction of tyrosine hydroxylase than of dopa oxidase activity in total cell extracts, and in the melanosomal and microsomal fractions. No evidence for the modulation of a tyrosinase effector was found. SDS-PAGE and specific activity stain demonstrated two forms of tyrosinase, with different degrees of induction by theophylline. These results agree with the recent proposal that two tyrosinases, encoded by different genes, are present in murine melanocytes.
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PMID:Melanocyte stimulating hormone activation of tyrosinase in B16 mouse melanoma cells. Evidence for a differential induction of two distinct isoenzymes. 135 58

Human melanoma cells (MM96E) were incubated with a phenotypic modifier (L-ethionine) to compare its effects on phenotypic expression with those induced by sodium butyrate and dimethyl sulfoxide. In contrast to the latter agents, L-ethionine (8mM) failed to arrest the cell cycle at the G1 phase or to inhibit colony formation ability after 48 hr incubation. Tyrosinase activity changed in parallel with 5-S-cysteinyldopa (5-S-CD) content during treatment with sodium butyrate or dimethyl sulfoxide. Tyrosinase was inhibited in L-ethionine-treated cells, probably because of metabolism of L-ethionine to sulfhydryl compounds; this remains to be clarified. Gamma-glutamyl transpeptidase activity changed inversely with tyrosinase activity after sodium butyrate or dimethyl sulfoxide incubation, whereas L-ethionine did not significantly alter the enzyme activity. In addition, only sodium butyrate induced alkaline phosphatase activity. L-ethionine was less effective than sodium butyrate or dimethyl sulfoxide in inhibiting expression of the B8G3 melanosomal antigen, as determined by Western blotting. These results suggest that phenotypic modifiers (differentiation inducers) affect melanoma cells in various ways and that melanogenesis therefore reflects only one aspect of differentiation in pigment cells.
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PMID:Alteration of melanoma melanogenesis by phenotypic modifiers. 136 29

Pigmentation of RVH 421 human melanoma cells is induced when cell division is inhibited by cytochalasin D or L-tyrosine phosphate. Increased pigmentation correlates with increased tyrosinase activity when this is monitored over a time-course. Parallel measurements show that the amount of tyrosinase mRNA correlates with enzyme activity in cells growing without these additives. In contrast, in the presence of cytochalasin D or L-tyrosine phosphate, the increase in amount of tyrosinase mRNA is not sufficient to account for the increase in enzyme activity, indicating that these compounds act mainly at a post-transcriptional level.
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PMID:Induction of tyrosinase in human melanoma cells by L-tyrosine phosphate and cytochalasin D. 137 60

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

To identify the cis-acting element that is responsible for the pigment cell-specific expression of the human tyrosinase gene, we analyzed the promoter activity of its 5'-flanking region by transient expression assays. The fusion genes were constructed by inserting the 5'-flanking region of the human tyrosinase gene upstream from the firefly luciferase gene and were introduced into human melanoma cells and HeLa cells. We thus found the element, located between 2.7 and 1.8 kilobase pairs upstream from the transcription initiation site, that enhances the transient expression of the luciferase reporter gene in melanoma cells, but not in HeLa cells, the tyrosinase gene expression of which is not detectable. Using the fusion genes containing putative enhancer elements under the control of the heterologous simian virus 40 promoter, we identified the pigment cell-specific enhancer of approximately 200 base pairs (bp) between -2.0 and -1.8 kilobase pairs and localized the core sequence to a 39-bp region. This 39-bp core element was then confirmed to direct the melanoma cell-specific expression of the reporter gene under the tyrosinase gene promoter. We thus propose that this core element is responsible for the pigment cell-specific expression of the human tyrosinase gene.
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PMID:Identification of a cis-acting element that enhances the pigment cell-specific expression of the human tyrosinase gene. 140 Mar 79

We have identified two different mutations in the tyrosinase genes of Japanese patients with tyrosinase-negative oculocutaneous albinism (OCA). One is a single base insertion in the exon 2 of the tyrosinase gene that shifts the reading frame and introduces a premature termination codon (TGA) after the amino acid residue 298 (codon 316). The other is a G to A transition at residue 312, leading to a single amino acid substitution, arginine at position 59 (codon 77) to glutamine. The promoter activity of the patients' tyrosinase genes was evaluated in the cell-free transcription system prepared from pigmented melanoma cells, indicating that the patients' genes were accurately transcribed in vitro. It is therefore conceivable that the tyrosinase gene is expressed in their melanocytes. Furthermore, transient expression of the mutated genes indicates that the truncated tyrosinase or the tyrosinase containing glutamine 59 is unable to form melanin in melanocytes. We therefore propose that these mutations in the tyrosinase genes lead to a phenotype of tyrosinase-negative OCA.
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PMID:Molecular bases of tyrosinase-negative oculocutaneous albinism: a single base insertion or a missense point mutation in the tyrosinase gene. 140 45

The action of the marine furanoditerpenes, spongiatriol (SP) and episopongiatriol (ESP), were compared in two sublines of human melanoma cells (MM96E and MM96L) derived from the same metastatic lesion. MM96E had higher tyrosinase activity and lower expression of alkaline phosphatase but was otherwise indistinguishable from MM96L. SP and ESP treatment of both cell lines for 72 h at cytostatic doses inhibited B8G3 expression and tyrosinase activity but had little effect on the expression of tyrosinase antigen. MM96L cells were affected more than MM96E. SP and ESP induced apoptosis in both cell lines, ESP causing dendritic morphology in a proportion of MM96L cells. SP induced a marked G2/M arrest in MM96E cells. SP and ESP together define subtle qualitative and quantitative differences in human melanoma phenoypes, possibly based on expression of a repertoire of neurotransmitter receptors.
Melanoma Res
PMID:Isomers of a marine diterpene distinguish sublines of human melanoma cells on the basis of apoptosis, cell cycle arrest and differentiation markers. 142 91

A model system for testing the efficacy of chemotherapy protocols for metastatic melanoma was established using cell cultures from two brain and three lymph node metastases of melanoma from five different patients. Continuously growing cultures which were positive for tyrosinase activity were analysed regarding their proliferation rate by continuous bromodeoxyuridine (BrdU) labelling and subsequent Hoechst-33258/ethidium bromide flow cytometry. Melanoma cell cultures exhibit a strong sensitivity to BrdU: at 5% oxygen, 50% growth inhibition is attained with 360 +/- 130 microM BrdU (range: 130-520; n = 11) vs 650 +/- 50 microM BrdU (n = 3) for diploid human fibroblasts and 570 +/- 20 microM BrdU (n = 6) for human lymphoid cell lines. Moreover, BrdU sensitivity of melanoma cells is clearly oxygen dependent: 50% growth inhibition at 200 +/- 55 microM (range: 65-400 microM) for 20% oxygen vs 360 +/- 130 microM BrdU for 5% oxygen. The cell cycle kinetic mechanism of BrdU-induced growth inhibition is accumulation of cells in the first cycle G2 phase. On the basis of these results we suggest testing BrdU in chemotherapy protocols for the treatment of metastatic melanoma.
Melanoma Res 1992 Nov
PMID:Bromodeoxyuridine hypersensitivity of metastatic melanoma cells. 149 Jan 11

The antifungal reagent Fungizone (amphotericin B and deoxycholate) caused an activation in dopachrome tautomerase and dopa oxidase activities of B16/F10 melanoma cells at the routine concentration (2.5 micrograms/ml) used for preventing molds and yeast growth in cultures of animal cells. However, higher amphotericin B concentrations caused a significant cell death and the inhibition of enzymatic activities. At the optimal concentration of Fungizone, the enzymatic activities and melanin content were augmented as incubation time increased. The detergent sodium deoxycholate alone exerted no effect on these melanogenic parameters, eliminating the possibility that this detergent was partially responsible for melanogenic modifications produced by Fungizone. After withdrawal of Fungizone from the reaction medium, the recovery of melanogenic parameters to normal values was slower for DCT than for tyrosinase. The behavior of dopa oxidase was very similar to that reported by Johnson and Bagnara (Pigment Cell Res. 3, 173-175) for tyrosine hydroxylase.
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PMID:Effect of amphotericin B on dopachrome tautomerase activity and other melanogenic parameters in cultured B16/F10 melanoma cells. 149 75

The tyrosinase gene is specifically expressed in melanocytes. Understanding the molecular basis of tissue-specific expression of the tyrosinase gene will greatly explain the mechanisms controlling pigmentation. We report a nucleotide sequence, TGATGTATTC, located -236 base pairs upstream of the transcription start site, that enhances tyrosinase gene expression in mouse melanoma cells. The sequence is referred to as the tyrosinase element-1 (TE-1). TE-1 was protected from DNase I cleavage by pigment cell nuclear extracts but was not protected by non-pigment cell nuclear extract. Partial purification of TE-1 binding protein (TEBP-1) was performed from the B16 mouse melanoma cell nuclear extract using biotin-cellulose affinity chromatography. The affinity-purified fraction exhibited binding to the DNA fragment containing TE-1, and to a synthetic oligomer representing TE-1. UV-cross-linking indicated that the size of TEBP-1 is approximately 49 kD. TE-1 also directed enhanced CAT activity in the B16 melanoma cells but not in non-pigment cells. These data indicate that TE-1 may be an enhancer element that is responsible for pigment cell specific expression of the tyrosinase gene.
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PMID:A cis-acting element involved in mouse tyrosinase gene expression and partial purification of its binding protein. 149 37


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