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

In culture, B16/C3 murine melanoma cells grown in the presence of serum undergo melanogenesis at a specific time after plating. At this time, melanin is synthesized intracellularly and then secreted into the extracellular culture fluid. We have found that melanin secretion is dependent on the presence of serum in the growth medium. When confluent cultures are deprived of serum, that is, refed with serum-free medium, cells remain viable but do not undergo melanogenesis. Addition of serum-free medium supplemented with either melanocyte-stimulating hormone (MSH) or dibutyryl cAMP induced melanogenesis in these cells but did not result in melanin secretion. Furthermore, when B16/C3 cells are grown in serum-free, hormone-supplemented medium, they also undergo melanogenesis but fail to release melanin. The addition of serum, however, to B16/C3 cells induced to undergo melanogenesis with MSH, dibutyryl cAMP, or hormone-supplemented medium promotes melanin secretion. Fractionation studies hence revealed that serum contains specific factors capable of inducing melanin secretion. These results demonstrate that factors that regulate melanin synthesis are distinct from those that induce cells to release melanin into their extracellular environment. Furthermore, the ability to induce melanogenesis with single factors will permit us to study the precise sequence of events leading to differentiation in B16/C3 cells under chemically defined conditions.
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PMID:Control of melanin synthesis and secretion by B16/C3 melanoma cells. 629 30

Mouse B16 melanoma cells respond to melanocyte-stimulating hormone (MSH) or cholera toxin (CT) with an accumulation of cAMP. The kinetics and dose-response of MSH were examined in the B16 parent line and two cell clones derived from it that exhibited wheat germ agglutinin (WGA) resistance [1]. These WGA lectin-resistant cells, designated W4 and W5 showed a greater response to MSH and CT than the parent B16 cells. Exposure of the W4 and W5 cells to lotus lectin or ricin respectively, led to the previously described [2] selection of cell clones that were resistant to lotus lectin (W4L) and ricin (W5R). The W4L and W5R cells which were shown [2] to be as sensitive as the B16 parent to WGA (i.e., were phenotypically reverted to WGA sensitivity), were also found to respond to MSH in a manner similar to the B16 parent. Since lectin sensitivity has been directly correlated in these cell clones with the membrane's oligosaccharides and glycopeptide pattern, these data suggest that the cellular binding and/or biological response to hormones is influenced by the carbohydrate composition of the plasma membrane.
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PMID:Lectin-resistant B16 melanoma cells exhibit an altered response to MSH and cholera toxin. 631 64

The level of cAMP was investigated in the following three types of hamster malignant melanomas: amelanotic, depigmented and melanotic. The amelanotic and depigmented tumors were undifferentiated, with high proliferative activity, and lacked tyrosinase. The melanotic one was slow growing, highly differentiated, and expressed tyrosinase activity. Among the melanomas investigated, the higher concentration of cAMP was found in undifferentiated tumors. The single treatment of the tumor-bearing animals with theophyllin or isoproterenol did not change the cAMP level in melanotic tumors, but significantly enhanced the cAMP content in amelanotic and especially depigmented melanomas. Multiple theophyllin treatment of tumor-bearing animals caused elevation of cAMP content in all tumors, but this effect was accompanied by enhancement of tyrosinase activity only in melanotic melanoma.
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PMID:Effect of theophyllin and isoproterenol on cAMP level in melanotic and amelanotic hamster melanomas. 631 98

Insulin lowers basal levels of tyrosinase activity and inhibits the MSH-induced increase in tyrosinase in Cloudman S-91 mouse melanoma cell cultures. Insulin exerts its inhibitory effects in a typical dose-response manner, with maximal inhibition of enzyme activity occurring at 10-7 M. At maximal inhibition, tyrosinase activity is reduced to approximately 50% of the control levels. This inhibition precedes the observed inhibitory effect on cellular proliferation. Insulin not only lowers cell responsiveness to MSH, but also inhibits the tyrosinase stimulation produced by either theophylline or (Bu)2cAMP. Neither control levels nor MSH-mediated elevated cellular levels of cAMP were altered by insulin (10-7 M). These findings suggest that insulin exerts its inhibitory effects at a site distal to cAMP production. The inhibitory effect of insulin on tyrosinase activity could not be mimicked by either (Bu)2cGMP or 8-bromo-cGMP, suggesting that insulin does not exert its effects by altering cellular levels of this nucleotide. Insulin reduces the rate of incorporation of [3H]leucine into trichloroacetic acid-precipitable material by 50%, a finding which suggests that insulin may exert its inhibitory effects on tyrosinase activity and perhaps on cellular proliferation by causing a general reduction in protein synthetic rates.
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PMID:Insulin-mediated inhibition of tyrosinase activity and protein synthesis in melanoma cell cultures. 631 45

Insulin inhibits the proliferation of wild-type Cloudman S91 mouse melanoma cells. The effects, which are mediated through specific, high-affinity receptors for insulin, appear to involve interactions with the cAMP system. Our evidence is as follows: 1) Cloudman cells have a cAMP requirement for proliferation and pigmentation. Exposure of cells to insulin results in a lowering of intracellular cAMP levels and inhibition of both cell division and pigment formation. 2) The effects of insulin are reversed by agents which raise cAMP levels, or by the cAMP analogue dibutyryl cAMP. 3) A mutant cell line with a temperature-dependent requirement for cAMP is most sensitive to the growth inhibitory effects of insulin when its requirements for cAMP are maximal. 4) Mutants selected only for alterations in their response to insulin frequently have concomitant alterations in their cAMP systems. 5) The melanotropin-responsive adenylate cyclase system is stimulated following prolonged exposure of cells in culture to insulin. Although we do not know the mechanism(s) for the interactions between the insulin and the cAMP system, our initial findings suggest that protein phosphorylation/dephosphorylation reactions are involved.
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PMID:Interactions between insulin and the cyclic AMP system of Cloudman S91 mouse melanoma cells. 631 5

We have previously reported [(1980) J. Biol. Chem. 255, 5999-6002] that retinoic acid inhibited growth and increased cyclic-AMP-dependent protein kinase activity in mouse melanoma cells. A variant melanoma line having depressed levels of cyclic-AMP-dependent protein kinase was not growth-inhibited by retinoic acid. In this report we describe the effect of retinoic acid on cyclic AMP binding proteins in B16 mouse melanoma cells. Using the technique of photoaffinity labeling, we found three major proteins of Mr 49 000, 52 000, and 55 000 which were specifically labeled with 8-N3-[32P]AMP in both control and treated cells. Based upon their molecular weight, relative affinity for 8-N3-[32P]AMP and comigration with standards, we have designated the 49 000-Mr and 55 000-Mr species as RI and RII respectively. The position of the intermediate band (Mr 52 000) was not affected by pre-incubation with ATP or alkaline phosphatase, and two-dimensional gel analysis indicated that it had the same pI as RI. Retinoic acid increased the 8-N3-[32P]AMP labeling of RI within 24 h, reaching a maximal six fold increase by 48 h. These increases were limited to the 40 000 X g supernatant fraction and occurred prior to any growth inhibition. By using increasing concentrations of 8-N3-cAMP we were able to construct a saturation curve for RI binding. Calculation of apparent Kd values from these curves showed nearly identical affinities for RI binding of 8-N3-cAMP from control and retinoic-acid-treated cells. Therefore we conclude that retinoic acid is increasing the amount of RI rather than altering its properties. Corroboration of these results was obtained by DEAE-cellulose chromatography. Peak I (corresponding to type I protein kinase) from retinoid-treated cells was increased about six fold in binding activity.
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PMID:The effect of retinoic acid on cyclic-AMP-binding proteins in mouse melanoma cells. 669 18

The mouse melanoma cell line B16/C3 offers an excellent in vitro model for studying melanocyte differentiation. Melanogenesis can be induced by serum, a hormone-supplemented serum-free medium, melanocyte stimulating hormone, and dibutyryl cAMP. The tumor promoter, 12-O-tetradecanoyl-phorbol-13-acetate, 5-bromodeoxyuridine, and acidic pH inhibit this process. Using two-dimensional polyacrylamide gel electrophoresis, we have identified four cellular proteins whose production is modulated during melanogenesis, a process which includes concomitant increases in levels of tyrosinase, the rate limiting enzyme for melanin biosynthesis, melanization, and ultimately, cell death. The production of these proteins are coordinately expressed or inhibited in response to the diverse inducers and inhibitors of melanogenesis. We conclude from these studies that these specific proteins are intimately involved in the differentiation of B16/C3 melanoma cells.
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PMID:Specific protein production during melanogenesis in B16/C3 melanoma cells. 682 62

We employ the murine S91 and the human Hs939 melanoma cell lines for the characterization of various biochemical changes induced by retinoids. Retinoic acid (RA) causes a time-dependent, and reversible reduction in cell proliferation rate in liquid medium and inhibits growth in agar. The proportion of cells in the G1 phase of the cell cycle increases in RA-treated cells, and the uptake of TdR, UdR and Leu decreases. The growth inhibitory effect of RA is apparently not mediated via labilization of lysosomes, increase in cAMP or changes in the synthesis of prostaglandins or polyamines. Exposure to RA stimulates tyrosinase activity and increases melanin content severalfold over the levels found in untreated cells. Various retinoids exhibit the activities of RA; however, their potencies vary depending on their structure. Those possessing a free -COOH at C-15 are usually more effective than those with a different group or with a derivatized carboxyl. A positive correlation exists between the ability of retinoids with a free -COOH in C-15 to inhibit growth and to bind to an RA-binding protein found in the S91 melanoma cells. Future studies will explore recently discovered changes in the glycosylation of cell surface components and their relationship to the phenomena described here.
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PMID:Characterization of retinoic acid-induced alterations in the proliferation and differentiation of a murine and a human melanoma cell line in culture. 694 72

When cultured in the presence of 2.0 microCi/ml (methyl-3H)thymidine (3H-TdR) the growth rate of 6 human melanoma lines and 1 subline progressively slowed then stopped, a change that was accompanied by loss of reproductive viability as assessed by colony formation in agar, but unaccompanied by a comparable inhibition of thymidine incorporation. In all cases increases in cell size, nuclear size and DNA content were observed. In 1 cell line only, MM96, these changes were accompanied by a profound increase in morphological differentiation. Despite this MM96 did not show increased differentiation in response to 2 x 10(-7) M alpha melanocyte stimulating-hormone (alpha MSH), which in fact stimulated growth, or in response to 10(-3) M N6,O2'-dibutyryl adenosine 3':5'-monophosphate (db-cAMP), 10(-3) M theophylline or 5 x 10(-4)M guanosine-5'-triphosphate (GTP), all of which retarded growth. With none of the cell lines was differentiation increased in response to 10(-3)M db-cAMP although in each case growth was retarded. These results reinforce the importance of colony assays vs DNA synthesis studies in assessing reproductive viability and show that supra-reproductively lethal levels of 3H-TdR can by-pass defects in the differentiation pathway of at least one, but not all, human melanoma cell lines.
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PMID:Tritiated-thymidine-induced increased DNA content and irreversible differentiation in a human melanoma cell line. 724 71

The pineal hormone melatonin modulates constitutive protein secretion from melanoma M2R cells. Nanomolar concentrations of melatonin inhibited protein secretion early after plating or at low cell density, but facilitated it late after plating or at high cell density. Inhibition by melatonin of adenylate cyclase is the best known downstream response to melatonin. We have therefore examined the involvement of cAMP in the melatonin-mediated modulation of protein secretion from the melanoma cells. Melatonin slightly but significantly reduced cell cAMP content when effecting inhibition and marginally increased cAMP levels when effecting facilitation of protein secretion. Dibutyryl cAMP abrogated the melatonin-mediated inhibition but not facilitation of protein secretion without affecting basal secretion. Accordingly, forskolin prevented the inhibitory action of melatonin on protein secretion without affecting basal secretion. The selective protein kinase A inhibitor H-89 did not alter the inhibitory effect of melatonin at low cell density and slightly facilitated secretion at high cell density with or without melatonin. Thus, melatonin's effects on protein secretion may not be mediated via cAMP. Nevertheless, changes in cAMP or protein kinase A activity can abrogate, or mask, the melatonin-mediated responses.
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PMID:Modulation by melatonin of protein secretion from melanoma cells: is cAMP involved? 748 20


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