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

We have previously shown that the retinoic acid (RA)-induced growth arrest and differentiation of B16 mouse melanoma cells is accompanied by a large increase in the amount and activity of protein kinase C (PKC). Since PKC is a multigene family, we investigated which isoforms were expressed in control and RA-treated B16 melanoma cells, and characterized the manner by which RA regulates PKC gene expression. We found that RA treatment of B16 cells resulted in an increase in PKC alpha mRNA beginning at 4-8 h and reached a maximum of 10- to 12-fold over control levels by 48 h. There was also a small amount of PKC gamma mRNA, present only in 48-h RA-treated cells, but no PKC beta mRNA was detected. The effect of RA on PKC alpha mRNA induction was not direct since the induction was abolished when cycloheximide was included in the incubation medium. Nuclear run-on experiments showed that the RA-induced increase in PKC alpha steady-state mRNA was not entirely due to an increase in transcriptional activity, as the increase in PKC alpha transcription was only 2- to 3-fold over control, which is not enough to account for the 10- to 15-fold increase in steady state levels. There was also no change in PKC alpha mRNA stability in RA-treated B16 cells compared to untreated cells. The 10.9-kb PKC alpha message in both control and RA-treated cells was less stable than the 3.8-kb PKC alpha message. Therefore, we propose that the major level of control of PKC alpha mRNA levels by RA is post-transcriptional, either RNA processing or transport out of the nucleus.
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PMID:Regulation of protein kinase C gene expression by retinoic acid in B16 mouse melanoma cells. 155 Mar 38

Human epidermal melanocytes were examined for proliferation under various conditions in the presence or absence of all-trans retinoic acid (RA). Under conditions which supported proliferation, RA at concentrations of 0.25-1.0 microgram/ml inhibited cell growth but was not cytotoxic. When melanocytes were cultured under conditions which by themselves did not support growth, RA did not overcome the growth limitation. Treatment of melanocytes with RA altered their morphological appearance. Alterations included retraction of dendritic processes, increased flattening, and a slight darkening of the cytoplasm in some of the cells. However, when examined biochemically, there was no significant change in the amount of malanin per cell or in tyrosinase activity. RA also inhibited proliferation of six different malignant melanoma lines. Inhibition was observed over the same RA concentrations and over the same time course in the melanoma cells as was seen in melanocytes. Inhibition of melanocyte and melanoma cell proliferation was slowly reversed following removal of RA from the culture medium. These results indicate that RA can inhibit proliferation of melanocytic cells.
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PMID:Modulation of growth in normal and malignant melanocytic cells by all-trans retinoic acid. 155 64

Differentiation of B16 mouse melanoma cells induced by retinoic acid (RA) is preceded by a large increase in protein kinase C alpha (PKC alpha) mRNA and protein. To determine the role of PKC alpha in the differentiation program, we stably transfected B16-F1 cells with a plasmid containing the full length PKC alpha cDNA driven by an SV40 promoter. Two out of thirty-two colonies screened were determined to overexpress PKC by 2-4-fold according to Western blot analysis and PKC enzyme activity. When compared to control cells (wild-type cells and cells transfected only with the neomycin resistance gene), PKC alpha overexpressing clones displayed longer doubling times, diminished anchorage-independent growth, and increased melanin production. RA treatment of control cells mimicked these phenotypic characteristics. When injected subcutaneously into syngeneic mice, PKC alpha overexpressing clones produced smaller tumors and had longer latencies than control cells. These findings, combined with the fact that phorbol esters down-regulate PKC and antagonize RA action suggest that PKC alpha plays a key role in the RA-induced melanoma differentiation.
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PMID:Increased expression of protein kinase C alpha plays a key role in retinoic acid-induced melanoma differentiation. 161 38

It is well documented that activated macrophages, but not nonactivated ones, kill tumor cells in vitro without damaging normal cells. We, however, have previously shown that embryo-derived teratocarcinoma cells (F9, P19, PCC4) are efficiently killed by nonactivated macrophages as well as by activated ones. Whereas other tumor cells are killed extracellularly by macrophages, we found that F9 teratocarcinoma cells are phagocytosed alive by macrophages and subsequently killed intracellularly by a process dependent on intact lysosomal function. Neither the H-2 antigens nor the mRNAs for the alpha-chain and beta 2-microglobulin are detectable in embryo-derived teratocarcinoma cells. An obvious explanation for this unique killing is that the nonactivated macrophages recognize and kill these cells due to their lack of class I MHC antigen expression, assuming that class I MHC gene products on the target cells switch off the cytolytic machinery of nonactivated macrophages. Our present findings demonstrate that there is no correlation between H-2 antigen expression on tumor cells and their susceptibility to killing by macrophages. Retinoic acid-differentiated F9 cells and P19 cells expressing H-2 antigen after exposure to MAF (IFN-gamma) were sensitive to the killing by nonactivated macrophages. Hybrids that arose from fusion of P19 teratocarcinoma cells with embryonal normal fibroblasts (C57BL/6), which displayed the morphology of embryonal carcinoma stem cells and expressed H-2 antigens, were also sensitive to the killing by nonactivated macrophages. On the other hand, the H-2-negative testicular 402AX teratocarcinoma cells and K1735P melanoma cells were both resistant to the killing by nonactivated macrophages. We concluded that the unique killing of embryo-derived teratocarcinoma cells by nonactivated murine macrophages is not related to a lack of H-2 antigen expression.
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PMID:The unique killing of embryo-derived teratocarcinoma cells by nonactivated murine macrophages is not due to a lack of H-2 antigen expression. 162 57

Melanin, the natural pigment found in human skin, absorbs and protects against the ultraviolet (UV) components of sunlight. Melanin production (melanogenesis) is increased by exposure to sunlight, causing a darker skin colour which is regarded as aesthetically pleasing by many humans, who therefore expose themselves to large amounts of potentially damaging sunlight. We have found that topically applied all-trans retinoic acid, a metabolic derivative of vitamin A, greatly enhances UV light-induced melanogenesis: the same preparation on its own had no effect on skin pigmentation. An orally administered retinoid, temarotene, did not have this effect. These observations were made using a lightly pigmented mouse strain, HRA: Skh-2, and confirmed in 2 human volunteers. This is the first time that metabolic derivatives of vitamin A have been shown to augment UV light-induced melanogenesis, suggesting a role for vitamin A in this process.
Melanoma Res 1992 May
PMID:Topical retinoic acid augments ultraviolet light-induced melanogenesis. 164 23

B16 mouse melanoma cells are grown inhibited by cyclic AMP or by retinoic acid (RA). However, the combination of these two agents results in less growth inhibition than either agent alone. In order to investigate this interaction, cells were selected for resistance to 8-bromo-cyclic AMP-induced growth inhibition. Two clones (3 and 7) which demonstrated significant resistance were isolated. When these two clones were treated with retinoic acid (RA) it was observed that they also exhibited different degrees of resistance to this growth inhibitor. This cross-resistance did not appear to be due to a lack of uptake or retention of the respective inhibitors, since the mutants took up and retained more 3H-cAMP and 3H-RA than wild type cells, suggesting that the dual resistance was not due to an amplification of P-glycoprotein. The mutation confering cAMP-resistance did not appear to involve cyclic AMP-dependent protein kinase, since both catalytic activity and the amount of cAMP protein binding was similar in wild type and mutants. Thus, the mutation must be beyond the interaction of cAMP with cAMP-dependent protein kinase. We have previously reported that RA induces protein kinase C in B16 melanoma cells (Niles and Loewy: Cancer Res. 49:4483-4487, 1989). Therefore, we measured the ability of RA to induce protein kinase C in the cyclic AMP-resistant mutants. We found an inverse correlation between RA-induced protein kinase C activity and growth inhibition in these mutants. The data reported here suggest that cyclic AMP regulates some step in the RA signal transduction pathway.
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PMID:B16 mouse melanoma cells selected for resistance to cyclic AMP-mediated growth inhibition are cross-resistant to retinoic acid-induced growth inhibition. 164 60

Two lines of murine melanoma cells (B16 and Cloudman S91) were cultured on type I collagen gel and the effects of all-trans-retinoic acid on the growth and infiltration into the gel were assayed. In both lines, proliferation and the degree of infiltration were suppressed by the addition of all-trans-retinoic acid. The infiltration-inhibiting effect was expressed very rapidly and was dose-dependent at concentrations ranging from 10(-7) to 10(-5) M of all-trans-retinoic acid. These results suggest the anti-invasive effects of all-trans-retinoic acid on melanoma cells.
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PMID:Effect of retinoic acid on the infiltration of murine melanoma cells into the type I collagen gel. 167 13

In a group of four human tumor cell lines comprising one melanoma, one glioma, one teratocarcinoma and one neuroblastoma, the expression of the intercellular adhesion molecule-1 (ICAM-1) was found to be significantly increased following treatment with 10 microM of all-trans retinoic acid. In the melanoma and glioma cell lines HS 294T and HS 683, greater than 90% of the cells reacted with the anti-ICAM-1 monoclonal antibody (mAb) CL203.4 in the absence of treatment. Retinoic acid increased the cell surface expression of the molecule by 2-fold. In the teratocarcinoma and neuroblastoma cell lines, TERA-2 and SK-N-SH, the constitutive expression of ICAM-1 was weak, the percentage of cells stained above the background being less than 25%. Retinoic acid induced ICAM-1 expression in greater than 80% of the cells and increased the levels of expression by 2.5 to 3-fold. Immunoprecipitation studies in biosynthetically labeled cells as well as RNase protection analysis confirmed that retinoic acid treatment increased the amount of ICAM-1 at both the protein and mRNA level. The induction or stimulation occurred within 24 h, was maximal after 4 days and reversible.
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PMID:Regulation by retinoic acid of ICAM-1 expression on human tumor cell lines. 168 Mar 99

Retinoic acid, hexamethylene bisacetamide, sodium butyrate, and dimethylsulfoxide, four compounds which modulate phenotypic expression in a variety of neoplastic cell lines, all inhibited the induction of tyrosinase activity and melanogenesis by the combination of melanocyte-stimulating hormone and isobutylmethyxanthine in Cloudman S91 melanoma cells. Results were the same in assays of whole cells or in extracts made from them. Only retinoic acid, however, was effective at inhibiting the activation of dopachrome isomerase, another regulatory enzyme in melanogenesis. Despite inhibiting the effects of melanocyte-stimulating hormone (MSH) and isobutylmethylxanthine on tyrosinase activity, all of the agents tested increased the binding of MSH to intact cells. Ultrastructural analysis of treated cells following DOPA cytochemistry revealed that both retinoic acid and hexamethylene bisacetamide arrested melanosomal maturation at stage I-II. Retinoic acid resulted in a derangement of melanosomal structure. The specificity of these agents for preventing the induction of melanogenesis makes them powerful tools for the dissection of this complex cellular process.
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PMID:Inhibition of induced melanogenesis in Cloudman melanoma cells by four phenotypic modifiers. 170 21

The effect of pretreatment of metastatic B16 melanoma cells with 10(-6) M all trans-retinoic acid resulted in a significant inhibition of lung colonization following injection of 10(5) cells into the tail vein of syngeneic C57BL mice. Adhesion of melanoma cells to vascular endothelial cell monolayers, and subendothelial extracellular matrix was also inhibited by pretreatment with retinoic acid, as was tumour cell aggregation following seeding of pretreated cells on to 0.5% agar. Release of 35SO4 from radiolabelled subendothelial extracellular matrix by melanoma cells was essentially unaltered by retinoic acid pretreatment, as was the release of radiolabel from [3H]proline-labelled matrix, while plasminogen activator activity was enhanced in retinoic-acid-treated cells. These observed changes in adhesive properties may be responsible, at least in part, for the retinoic-acid-induced inhibition of lung colonization.
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PMID:Retinoic acid-induced inhibition of metastatic melanoma cell lung colonization and adhesion to endothelium and subendothelial extracellular matrix. 173 48


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