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)

The acute in vitro action of adrenocorticotropin (ACTH) and corticosterone alone and in combination were determined in the Cloudman S-91 melanoma grown in vivo. Hormone-treated melanoma dice (5-240 min) were analyzed for tyrosinase activity (EC 1.14.18.1), cyclic AMP (cAMP) and cyclic GMP (cGMP). ACTH elevated cAMP levels in the S-91 melanoma. However, these increases in cAMP were not accompanied by increased tyrosinase activity. Corticosterone depressed cAMP levels while stimulating tyrosinase activity. ACTH plus corticosterone produced an early cAMP peak followed by depression. ACTH plus corticosterone stimulated tyrosine activity coincident with the early cAMP peak followed by a drop in tyrosinase activity which was subsequently elevated. cGMP levels were not altered by any hormone treatment. The results indicate that cAMP is not the sole modulator of tyrosinase activity and suggest the interaction of ACTH, corticosterone and cAMP in the regulation of melanoma tyrosinase activity.
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PMID:Glucocorticoid modulation of adrenocorticotropin-induced melanogenesis in the Cloudman S-91 melanoma in vitro. 20 85

A stimulation of the tyrosinase activity was observed when melanoma cells isolated from transplantable mouse melanomas were incubated at 37 degrees C for 6 h in the presence of 1-10 X 10(-6) M alpha-MSH. All strains of mouse melanomas studied (B-16, Cloudman S-91 and Harding-Passey), exhibited similar responses. It was also observed that the intact cellular structure of melanoma cells was not required for the ability to respond to alpha-MSH. The stimulation of the enzymic activity was accompanied by an increase of the rate of incorporation of radioactivity into melanin from L-[U-14C]tyrosine, indicating an enhanced melanogenesis of tumour cells under in vitro conditions.
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PMID:Effect of alpha-MSH on the tyrosinase activity and the rate of melanin accumulation of melanoma cells in vitro. 40 59

Human malignant melanocytes show characteristic morphologic modifications which are particularly evident in their specific organelles: melanosomes. These modifications are conserved in cell culture. The ultrastructural localization of tyrosinase, the enzyme which converts tyrosine and dopa into melanin, was determined in 13 human melanoma cell lines. The different cell lines possess 4 distribution patterns of melanin synthesis based on dopa oxidase activity. The two first pathways, which involve the Golgi apparatus, seem to differ by the amount of enzyme within this organelle. The third pathway mainly involves the smooth endoplasmic reticulum, whereas tyrosinase is visible only in vesicles in the fourth. Some cells synthesize the enzyme in the manner observed in very early embryos.
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PMID:Cellular localization of tyrosinase in human malignant melanoma cell lines. 40 30

Serum tyrosinase activity has been measured by adapting the [3]tyrosine assay for tyrosinase and significant elevations of serum tyrosinase activity were found in patients with malignant melanoma. In contrast to findings in a study which utilized [14C]tyrosine, augmented levels of tyrosinase activity were not observed in sera from patients with other malignancies, including subjects with carcinoma of the breast. The results of the examinations for soluble tyrosinase activity in human malignant melanoma tissue-cultured lines were all positive, whereas human cell lines from carcinoma of the breast, carcinoma of the colon and sarcoma uniformly showed no activity. The method employed for detecting tyrosinase activity holds promise as a specific diagnostic test and may be valuable for monitoring the response to clinical treatment of patients with malignant melanoma.
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PMID:Tyrosinase activity in the sera of patients with malignant melanoma: method and specificity. 41 60

Hamster melanoma cells (RPMI 3460) were examined for their ability to utilize phenylalanine for melanin biosynthesis. There was a small but significant incorporation of L-[1-1414C] phenylalanine into hot acid-insoluble cellular material in the presence of cycloheximide. However, this radioactivity was removable from the acid-insoluble fraction by pronase digestion. A similar percentage of L-[U-14C] leucine incorporation was likewise resistant to cycloheximide inhibition. Residual protein synthesis is apparently responsible for the incorporation of both amino acids. Cycloheximide did not inhibit melanin synthesis. These results suggest that mammalian melanocytes do not use phenylalanine for melanin synthesis. Phenylalanine is not incorporated directly into melanin, nor do the cells appear to convert it to tyrosine via a phenylalanine hydroxylase.
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PMID:Mammalian melanocytes do not use phenylalanine for melanin synthesis. 55 59

Activity of arylsulphatase, beta-glucuronidase, cathepsin D, and acid phosphatase in the homogenates of melanotic and amelanotic melanoma was determined. The activity of these enzymes is higher in melanotic than in amelanotic melanoma. Respective values for melanotic and amelanotic tumours are: arylsulphatase 10,78 +/- 3,20, and 1,45 +/- 0,66 micron 4-nitrocatechole/mg protein/hr; beta-glucuronidase 11,10 +/- 1,40, and 9,98 +/- 1,35 micron phenolphthalein/mg protein/hr; cathepsin D 4,24 +/- 1,37, and 3,26 +/- 0,73 micron tyrosine/mg protein/hr; acid phosphatase 230 +/- 22, and 180 +/- 25 micron p-nitrophenol/mg protein/hr. These differences are statistically significant. The increased activity of the lysosomal enzymes in melantoic melanoma probably depends on the occurrence of an higher number of lysosomes in tissues containing melanins.
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PMID:Activity of some lysosomal hydrolases in the homogenates of transplantable melanotic and amelanotic melanoma in golden hamster (Mesocricetus auratus, Waterhouse). 68 81

Melanosomes isolated from a subcutaneous Harding-Passey mouse melanoma and purified by density gradient centrifugation were labelled in vitro with 14C-tyrosine or 3H-dihydroxyphenylalanine in the melanin portion. Incubation of monolayer cultures of Harding-Passey melanoma cells during exponential growth phase (wherin cells contained relatively few melanosomes) with isolated and labelled melanosomes during a time-period of up to 3 days resulted in rapid cellular uptake of label (reaching a saturation level after about half a day). Following a lag period of several hours, the melanin content rose near-linearly in the course of 3 days. Comparison of curves of uptake of radioactivity and melanin concentration indicates that the latter rise is due primarily to newly formed melanin. Ultrastructural studies revealed a strikingly increased number of melanosomes in melanosome-treated cells. Some of these appeared to be the result of phagocytotic uptake. In fact, invagigations of the plasma membrane containing exogenous melanosomes were observed. Since most intracellular melanosomes were localized directly in the cytoplasmic matrix, dissolution of the phagosome membrane appeared to have taken place. Aggregates of melanosomes either surrounded by a membrane or free in the cytoplasm were also observed. These bodies might represent phagolysosomes or/and centres for the formation of new melanosomes. The combined biochemical and ultrastructural findings suggest stimulated melanogenesis induced by phagocytized melanosomes.
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PMID:Uptake of melanosomes and increased melanin formation by cultured melanoma cells after treatment with isolated melanosomes. 75 76

The possibility that peroxidase is functional in melanogenesis in the murine S-91 melanoma has been investigated. It was found that, as in the normal mouse, tyrosinase is the enzyme responsible for the bulk of melanin formation in the malignant melanocyte. Tyrosinase was capable of utilizing tyrosine as a substrate, as well as dopa, although the Vmax with dopa was much higher than with tyrosine. Conversely, the affinity of the enzyme for tyrosine is higher than for dopa, and this relationship may in part be responsible for the occasional misinterpretation of the functional capability of this enzyme.
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PMID:Involvement of tyrosinase in melanin formation in murine melanoma. 80 29

Melanosomal "tyrosinase" (L-dopa) was isolated from trypsin digest of B-16 mouse melanoma melanosomes, using polyacrylamide gel disc electrophoresis. The enzyme was represented by a single band, having characteristics similar to the T1 dopa-positive band observed when using supernatants of crude melanoma homogenates as the source. When gels with this band were incubated in solutions containing tyrosine and dopa in varying ratios , there was no enhancement of melanin formation by tyrosine when compared with incubations in corresponding concentrations of dopa alone. These data further support previous studies in our laboratory demonstrating an inability of so-called mamalian "tyrosinase" to convert tyrosine to melanin; since this enzyme readily converts L-dopa to melanin, it seems more reasonable to term this enzyme an L-dopa oxidase.
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PMID:Inability of murine melanoma melanosomal "tyrosinase" (L-dopa oxidase) to oxidize tyrosine to melanin in polyacrylamide gel systems. 80 38

The biochemistry of malignant melanoma is reviewed. The biosynthesis of melanin from tyrosine is described and the role of tyrosinase and other enzymes in melanoma considered. Detailed methods for the assay of free catechols, their metabolites and urinary indole melanogens are included. Normal values for these constituents and their significance in the evaluation of melanoma patients are discussed.
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PMID:Biochemistry of malignant melanoma. 81 57


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