Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.10.3.1 (tyrosinase)
 9,065 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies of the human neuroblastoma cell line SK-N-SH had demonstrated the presence of and phenotypic interconversion (transdifferentiation) between two morphologically and biochemically distinct cell types: N (neuroblastic) cells with properties of noradrenergic neurons and S (substrate-adherent) cells with properties of melanocytes. Current studies have sought to test the generality of these findings among other cultured human neuroblastoma cell lines and to define further the S-cell phenotype and that of a newly identified, morphologically intermediate, I-type cell. Morphologically homogeneous populations (clonal sublines or subpopulations) of N, S, and I cells were isolated from five additional neuroblastoma cell lines and analyzed biochemically for neuronal, glial, and melanocytic marker enzyme activities and norepinephrine uptake. Immunoblot techniques were used to detect intermediate filament proteins (neurofilament protein, vimentin, glial fibrillary acidic protein) and fibronectin. All N-type cells exhibited neuronal marker enzyme activities, specific uptake of norepinephrine, and presence of one or more neurofilament proteins. S-type cells generally lacked neuronal characteristics but contained, instead, tyrosinase activity (a melanocytic marker enzyme), vimentin, and fibronectin. This combination of attributes is suggestive of a multipotent embryonal precursor cell of the neural crest. I-type cells differentially expressed both S- and N-cell properties and could represent either a stem cell or an intermediate in the transdifferentiation process. Studies of the biological significance of human neuroblastoma cell transdifferentiation and the molecular mechanisms underlying this process may be of relevance to the biological and clinical behavior of this tumor in the patient.
Cancer Res 1989 Jan 01
PMID:Phenotypic diversification in human neuroblastoma cells: expression of distinct neural crest lineages. 253 91

Infection of normal human melanocyte and nevus cultures with an adenovirus 12-Simian Virus 40 hybrid virus (Ad12-SV40) produced transformed cells that expressed SV40-T antigen. The Ad12-SV40 cells exhibited rapid cell proliferation to high cell densities and efficient growth in soft agar, but none of 15 transformed melanocyte and nevus cultures formed tumors when injected s.c. or under the renal capsule into athymic nude mice. While the Ad12-SV40-transformed cells lost certain properties associated with the melanocytic phenotype, i.e., pigmentation, tyrosinase activity and melanosome content, the expression of melanoma-associated antigens, including nerve growth factor receptor, p97 melano-transferrin, and chondroitin sulfate proteoglycan, remained stable. The transformed melanocytes acquired the ability to express HLA-DR antigen, which is found on nevus and melanoma cells. Total ganglioside patterns in Ad12-SV40-transformed cells changed to reflect more advanced stages of tumor progression. Transformed melanocytes, like nevus and melanoma cells, showed increased GD3 content and transformed nevus cells increased GD2 which is a feature of malignant melanoma cells. Ad12-SV40-transformed human melanocytes and nevus cells are useful tools for studying tumor progression under experimental conditions.
Int J Cancer 1989 Dec 15
PMID:Transformation of normal human melanocytes and non-malignant nevus cells by adenovirus 12-SV40 hybrid virus. 255 80

The various physiological effects of alpha-MSH, mainly on the CNS and on pigmentation in animal models, are well documented in the literature. Only a few investigators have confirmed similar properties in the human. However, the possible physiopathological role played by this hormone in human melanoma is still poorly defined. In order to approach this subject in a manner as complete as possible, we have performed, during the past four years, three different series of experiments: 1) alpha-MSH measurements in plasma samples from: a. melanoma and other cancer patients, b. whole body UVA irradiated healthy adults, c. circadian rhythm determinations in melanoma patients and in healthy male adults; 2) alpha-MSH measurements in human melanoma tumours; 3) alpha-MSH receptor expression on human melanoma cells in culture involving: a. alpha-MSH radio-binding assays and b. tyrosinase assay. Our results so far show 1) increased alpha-MSH levels in melanoma patients' plasma, alpha-MSH responsiveness to UVA stimulated skin, large immunoreactive alpha-MSH content in melanoma metastases and an alpha-MSH circadian rhythm in some individuals different from cortisol; 2) alpha-MSH receptor expression in melanoma cells could be increased by various effectors able to stimulate melanogenesis.
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PMID:Studies on factors influencing human plasma alpha-MSH. 256 Jun 23

A preparation procedure is presented for the determination of tyrosinase-catalysed stereo-specific dopa oxidase activity in serum. Purification is obtained by separation on a Phenyl-Sepharose hydrophobic interaction column, followed by Con-A-Sepharose chromatography. Five out of seven sera from patients with widespread melanoma metastases were found to contain detectable quantities of tyrosinase. There was no tyrosinase activity in seven sera from patients with other malignancies, nor in six other control sera from individuals without malignancies. One serum which showed high tyrosinase activity was processed as above and studied by SDS-PAGE. A dopa-reactive band with an apparent MW of 66 kD was present in the gel, i.e. at the same place as that of the soluble tyrosinase of cultured human malignant melanoma cells. The protein was found to have the same pI at isoelectric focusing, and eluted in the same way from the preparation columns used, as did soluble tyrosinase.
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PMID:Tyrosinase activity in serum from patients with malignant melanoma. 256 28

The biosynthesis, structure, and topology of a melanoma-associated antigen, previously defined with the monoclonal antibody NKI/C-3 was studied. A polyclonal rabbit antiserum was raised against the antigen with a broader reactivity than the previously used monoclonal antibody NKI/C-3. The antigen was shown to consist of a single protein backbone to which two or three N-linked glycans were added cotranslationally. Extensive further heterogeneity was generated in the Golgi compartment and was shown to be dependent on the presence of complex type sugars. Although the antigen is associated with melanomas, it was not codistributed with the tyrosinase activity associated with melanogenesis. The antigen did show codistribution with cathepsin D, which is a marker for lysosomal functions.
Cancer Res 1989 Jan 15
PMID:Structural heterogeneity of a human melanoma-associated antigen. 264 40

The purpose of these studies was to investigate the relationship of the host microenvironment to the metastatic and pigmented phenotypes of the SW-1 variant of the murine K-1735 melanoma. The SW-1 subline was isolated from an amelanotic lung metastasis in a C3H/HeN mouse given an s.c. injection of the K-1735 melanoma. Cells of this line were highly metastatic and produced tumor deposits in many organs. In all sites except the brain, these lesions were predominantly amelanotic. K-1735 SW-1 cells were isolated from metastases in various organs and subsequently reinoculated into normal syngeneic recipients. Whereas the metastatic phenotype remained stable and thus was heritable, pigmentation was unstable and appeared to be modulated by the site of tumor growth. Further differences in the phenotype of K-1735 SW-1 cells growing in vivo and in culture were revealed by assays for tyrosinase activity. K-1735 SW-1 cells growing in culture did not produce melanin nor did they respond to agents that can stimulate melanin production in another mouse melanoma, the B16 line. K-1735 SW-1 cells do not, however, lack tyrosinase, since these cells are capable of producing melanin when growing in certain organs in vivo. We conclude that the host organ environment may influence a phenotype of malignant melanoma cells, i.e., pigmentation. These findings also suggest caution when extrapolating the results of in vitro biochemical assays to properties of tumor cells growing in vivo.
Cancer Res 1988 Apr 15
PMID:Influence of organ microenvironment on pigmentation of a metastatic murine melanoma. 283 58

The melanocytotoxic effects of 4-hydroxyanisole (4-OHA) are thought to depend upon its conversion to toxic oxidation products by the enzyme tyrosinase. In this study, the cytotoxicity of 4-OHA was examined in different B16 melanoma cell lines that show varying levels of tyrosinase and after stimulation by melanocyte-stimulating hormone (MSH) and all-trans-retinoic acid (RA). 4-OHA decreased cell survival of three melanotic and one amelanotic cell line in culture, but the effect was unrelated to their tyrosinase activity or the subcellular localization of the enzyme. Although stimulation of tyrosinase activity with RA enhanced the cytotoxicity of 4-OHA, no similar enhancement occurred with alpha-MSH. It appears that there is no relationship between the cytotoxic effects of 4-OHA and intracellular tyrosinase and the enhancement of its cytotoxicity by RA may well be related to the antiproliferative effects of the retinoid.
Eur J Cancer Clin Oncol 1988 Dec
PMID:Cytotoxicity of 4-hydroxyanisole and tyrosinase activity in variant cell lines of B16 melanoma. 285 44

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.
Cancer Chemother Pharmacol 1989
PMID:Melanin synthesis and the action of L-dopa and 3,4-dihydroxybenzylamine in human melanoma cells. 290 84

Melanin synthesis of B16 mouse melanoma cells was found to be stimulated dose and time dependently by 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25(OH)2D3], the hormonal form of vitamin D3. The stimulation of melanogenesis resulted from an increase in the activity of tyrosinase, a key enzyme in melanin synthesis. The minimum dose required for this stimulation was as low as 0.05 ng/ml, or 0.12 nM, a physiological level of plasma 1 alpha,25(OH)2D3. The stimulation by 1 alpha,25(OH)2D3 was specific; other derivatives of vitamin D3 caused no stimulation at a concentration of 500 ng/ml. When the cells were plated on agar plates, the proportion of dark or black colonies was not increased by the exposure to 1 alpha,25(OH)2D3. Furthermore, this compound did not induce melanin synthesis of an amelanotic variant. Thus, its stimulatory effect seemed to be due to stimulation of melanin synthesis of melanotic cells, rather than to conversion of amelanotic clones to melanotic ones. 1 alpha,25(OH)2D3 did not induce intracellular cyclic adenosine 3':5'-monophosphate, while cholera toxin induced cyclic adenosine 3':5'-monophosphate and stimulated melanin synthesis and tyrosinase activity much more than did 1 alpha,25(OH)2D3, suggesting that 1 alpha,25(OH)2D3 stimulates melanin synthesis by a cyclic adenosine 3':5'-monophosphate-independent mechanism. B16 melanoma cells contained specific receptors for 1 alpha,25(OH)2D3. Scatchard plot analysis revealed two types of receptor; the high-affinity receptor had a Kd of 18.3 pM and an Nmax of 10.6 fmol/mg of protein. The specificity of receptor binding was demonstrated by studies showing that, for 50% displacement of 1 alpha,alpha,25(OH)2D3 binding, other derivatives were required at 500 times higher concentrations or more. In contrast to 1 alpha,25(OH)2D3, retinoic acid inhibited melanin synthesis and tyrosinase activity of B16 melanoma cells dose and time dependently. On simultaneous treatment, 1 alpha,25(OH)2D3 and retinoic acid caused mutual interference, and a balance between their respective stimulating and inhibitory effects was obtained at a molar ratio of 10:1; i.e., with 10 nM 1 alpha,25(OH)2D3 and 1 nM retinoic acid.
Cancer Res 1985 Apr
PMID:Regulation of melanin synthesis of B16 mouse melanoma cells by 1 alpha, 25-dihydroxyvitamin D3 and retinoic acid. 298 83

The human neuroblastoma cell line SK-N-SH comprises cells that undergo morphological and biochemical interconversion between a primitive sympathoblast and a variant, epithelial-like cell type which does not express the neuronal characteristics of the SK-N-SH cell line. Since neural crest cells, from which neuroblastomas are presumed to arise, can undergo transdifferentiation in culture from a neuronal phenotype into other cellular phenotypes, particularly into neurilemmal cells and melanocytes, the present study was undertaken to determine whether this capacity is preserved in malignant cells of the peripheral nervous system. Activities for tyrosinase, a melanocyte marker enzyme, and 2':3'-cyclic nucleotide phosphohydrolase, a Schwann-cell marker enzyme, were measured in clones of the two cell types. While no significant differences in 2':3'-cyclic nucleotide phosphohydrolase activity were measurable, tyrosinase activity was detectable only in the flattened neuroblastoma variant cell lines and was comparable to that in some human melanoma cell lines. The tyrosinase activity in neuroblastoma cell variants increased with cell density and was significantly elevated by melanocyte-stimulating hormone and 8-bromo-cyclic adenosine monophosphate, similar to that seen in melanoma cells in culture. Thus, our findings show that human neuroblastoma cells can undergo bidirectional transdifferentiation in vitro between a neuronal and a melanocyte phenotype, possibly reflecting a process which occurs in the patient.
Cancer Res 1985 Apr
PMID:Presence and regulation of tyrosinase activity in human neuroblastoma cell variants in vitro. 298 84


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