Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have found that three phenotypically dissimilar mouse B16 melanoma subclones are competent recipients for DNA-mediated gene transfer. Two of these approach and a third, amelanotic clone B78H1, surpasses mouse LTK cells in frequencies of transferent colony formation after treatment with either of two codominantly selectable plasmid vectors, pSV2gpt or pGCcos3neo. Melanoma transferents incorporate both selectable plasmid-homologous sequences and substantial amounts of unselected donor DNA into their cellular DNAs. In addition they retain the distinctive states of differentiation characteristic of the untreated clones. Frequencies of pGCcos3neo-mediated transfer of neo gene-encoded antibiotic resistance into B78H1 can reach 10(-2) in response to treatment with as little as 15 ng plasmid/ml coprecipitate/dish. B78H1 cells readily give rise to "secondary" transferents for the neo gene after treatment with DNA from a "primary" B78H1 neo transferent. This gene transfer system has potential applications for study of regulation of melanoma and neural crest differentiation and malignancy.
Somat Cell Mol Genet 1984 Mar
PMID:Efficient DNA-mediated transfer of selectable genes and unselected sequences into differentiated and undifferentiated mouse melanoma clones. 632 93

Interleukin-1 (IL-1) is a growth arrest signal for diverse human tumor cell lines. We report here that the action of this cytokine in melanoma cells is associated with induction of EGR-1, a zinc finger protein that activates gene transcription. Both growth arrest and EGR-1 are induced via the type I receptor of IL-1. To determine the role of EGR-1 in IL-1 action in melanoma cells, we used a chimera expressing the transrepression domain of the Wilm's tumor gene, WT1, and the DNA binding domain of Egr-1. This chimera competitively inhibited EGR-1-dependent transactivation via the GC-rich DNA binding sequence, indicating that it acted as a functional dominant negative mutant of Egr-1. Melanoma cell lines stably transfected with the dominant negative mutant construct were supersensitive to IL-1 and showed accelerated G0/G1 growth arrest compared with the parental cell line. The effect of the dominant negative mutant construct was mimicked by addition of an antisense Egr-1 oligomer to the culture medium of the parental cells: the oligomer inhibited EGR-1 expression and accelerated the growth-inhibitory response to IL-1. These data imply that EGR-1 acts to delay IL-1-mediated tumor growth arrest.
Mol Cell Biol 1995 Feb
PMID:The zinc finger transcription factor EGR-1 impedes interleukin-1-inducible tumor growth arrest. 782 37

Melanoma cell lines exhibit strikingly different sensitivity to the antiproliferative effects of interferon. cDNAs encoding the Type I interferon receptor subunit were amplified by polymerase chain reaction, using as template RNA isolated from three melanoma cell lines displaying greater than 100 fold range in their sensitivity to the antiproliferative effects of IFN-beta. Comparison of the cDNA sequences obtained with the published cDNA sequence from the highly interferon-sensitive lymphoid cell line Daudi revealed only one base change that leads to a conservative amino acid substitution. It is concluded that the cellular differences in responsiveness to interferon, of the melanoma cell lines tested, do not arise from the expression of variants of the cloned Type I interferon receptor subunit.
Biochem Mol Biol Int 1994 May
PMID:cDNA sequence identity for the type I interferon receptor subunit from cell lines of widely differing responsiveness to interferon. 795 Oct 47

The inhibition by different p-alkoxyphenol derivatives of the growth-regulating enzyme ribonucleotide reductase (RR) in purified Escherichia coli and mouse R2 protein preparations was studied by EPR spectroscopy. The inhibitor-induced inactivation of the catalytic subunit protein R2 was measured at 77 degrees K by observing the decrease of the typical EPR signal from the functionally essential protein-linked tyrosyl free radical. p-Methoxy-, p-ethoxy-, p-propoxy-, and p-allyloxyphenol were about 2 orders of magnitude more effective in inhibiting mouse R2, compared with E. coli R2. Among the p-alkoxyphenols studied, p-propoxyphenol was the most effective inhibitor of mouse R2 (IC50, 0.7 microM) and p-methoxyphenol was the least effective (IC50, 11 microM); p-ethoxy- and p-allyloxyphenol were intermediate. The observed half-maximal inhibition values characterized p-alkoxyphenols as a new class of strong inhibitors of the R2 protein of mammalian RR. p-Propoxy-, p-ethoxy-, and p-allyloxyphenol could be considered as new candidates for anticancer drugs. A special cellular inhibition assay of RR in proliferating tumor cells, in which the tyrosyl radical of R2 at natural concentration was monitored by EPR, showed that the four para-substituted alkoxyphenols also inhibited the enzyme with high efficiency in tumor cells (IC50, between 0.5 microM and 5 microM). Our results with inactivation of protein R2 of RR imply that the cytostatic effect of p-alkoxyphenols on melanoma cells, which has been hitherto explained by inhibition of tyrosinase [Melanoma Res. 2:295-304 (1992)], may be caused at least partly by inhibition of RR. Protein R2 of RR may be considered as an additional target that could be used for future cancer chemotherapy.
Mol Pharmacol 1994 Apr
PMID:p-Alkoxyphenols, a new class of inhibitors of mammalian R2 ribonucleotide reductase: possible candidates for antimelanotic drugs. 818 56

Melanoma is the prototype of a tumor to which many forms of immunotherapy have been applied extensively over the past two decades. Melanoma vaccines (active specific immunotherapy) are designed to modulate the immune system and have subsequent anti-tumor effects with minimal toxicity. Previous attempts to produce melanoma vaccines include immunization with whole tumor cells/cell lysates admixed with nonspecific adjuvants. While these vaccines generate enhanced anti-tumor immunity in a subset of patients, some of whom survive for longer than historical controls, no clinical benefit has so far been demonstrated in a properly controlled phase III study. Genetic modifications of tumor cells to make them express cytokines afford new-generation melanoma vaccines, and generate long-lasting systemic antitumor immunity in animal models. Translation of these preclinical results primarily into melanoma patients with advanced diseases shows the potential to induce systemic antitumor immune responses and in some instances tumor regression with acceptably low toxicity. The efficacy of this novel vaccine approach would be expected to be higher when used in a postsurgical adjuvant setting when the tumor load is small. Other novel vaccine approaches such as dendritic cell-based therapy also hold promise for the treatment of melanoma. The clinical value of all these new approaches will eventually have to be established in prospectively randomized clinical studies.
J Mol Med (Berl) 1999 Aug
PMID:Cell-based vaccination against melanoma--background, preliminary results, and perspective. 1054 91

Melanoma development involves processes determined collectively by various microenvironmental factors, among which intercellular communication has drawn increased attention. Cell-cell crosstalk mediated by cadherins and connexins results in coordinated regulation of cell growth, differentiation, apoptosis and migration. Abnormal expression of adhesion receptors and dysregulated intercellular communication appears to drive tumor development and progression.
Mol Med Today 2000 Apr
PMID:Dynamics of intercellular communication during melanoma development. 1074 Feb 55

Melanoma metastasis is almost uniformly fatal. The identification of signal transduction as crucial effectors for tumorigenesis suggests modalities of gene therapy as well as design of specific drugs. the possible use of nPKCdelta as a therapeutic target is reviewed and discussed. Motivated by recent results, we propose a model in which nPKCdelta modulates melanin synthesis as well as metastasis.
Int J Mol Med 2000 May
PMID:nPKCdelta a new therapeutic marker for melanoma metastasis? (Review). 1076 48

Interleukin (IL)-8 is a C-X-C chemokine that plays an important role in acute inflammation through its G protein-coupled receptors CXCR1 and CXCR2. In this study, we investigated the role of IL-8 as an autocrine regulator of IL-8 production and the signaling mechanisms involved in human peripheral blood mononuclear cells (MNCs). Sepharose-immobilized IL-8 stimulated a sevenfold increase in IL-8 production within 2 h. IL-8 induced the expression of its own message, and IL-8 biosynthesis was inhibited by cycloheximide and actinomycin D, indicating de novo RNA and protein synthesis. In contrast to MNCs, polymorphonuclear neutrophils did not respond to the immobilized IL-8 with IL-8 production despite cell surface expression of CXCR1 and CXCR2. Melanoma growth-stimulatory activity/growth-related protein-alpha (MGSA/GROalpha), which binds CXCR2 but not CXCR1, was unable to either stimulate IL-8 secretion in MNCs or desensitize these cells to respond to immobilized IL-8. The involvement of mitogen-activated protein kinase (MAPK) in IL-8-induced IL-8 biosynthesis was suggested by the ability of PD-98059, an inhibitor of MAPK kinase, to block this function. Furthermore, IL-8 induced a significant increase in extracellular signal-regulated kinase 2 phosphorylation, whereas MGSA/GROalpha was much less effective. These findings support the role of IL-8 as an autocrine regulator of IL-8 production and suggest that this function is mediated by CXCR1 through activation of MAPK.
Am J Physiol Lung Cell Mol Physiol 2000 Dec
PMID:Autocrine regulation of interleukin-8 production in human monocytes. 1107 3

Tumor necrosis factor (TNF) causes cell necrosis in vivo by damaging the endothelium of the neovasculature. However, its mechanism of action is not well understood. We hypothesized that TNF affects the tumor microenvironment even before neovascularization occurs, thereby increasing lymphocyte locomotion through the peritumoral matrix, a crucial step in tumor cell killing. The effect of TNF on lymphocytes was tested with the type I rat-tail collagen mini-assay in peripheral blood lymphocytes (PBL) from normal donors, a non-migratory PBL cell line (HPB), and a C3H mice splenic lymphocytes. Melanoma cell line (k1735p) was treated with TNFalpha/TNFbeta 10 or 20 pg/microl. The syngeneic splenic lymphocytes were layered on top of the collagen, and their migration into the collagen towards the tumor cells was assessed. Tumor cell viability was evaluated before and after TNF treatment. Paired two-tailed Student's t-test was used for statistical analysis. TNFalpha and TNFbeta had no significant direct effect on locomotion of PBL or HPB. Lymphocyte locomotion was inhibited in the presence of untreated melanoma cells in 7 of 9 assays (statistically significant in four), and it was significantly increased towards TNFalpha- or beta-treated melanoma cells, compared to untreated condition, in 7 of 9 assays (p=0.05 to p=0.0001). The number of viable tumor cells was not significantly different before and after treatment. In conclusion, treatment of tumor cells with TNFalpha or TNFbeta significantly enhances lymphocyte locomotion through the matrix. The effect of TNF is not the result of a direct influence on the lymphocytes, and is not associated with a decrease in the number of viable tumor cells. These findings suggest that TNF interaction with the cell microenvironment induces a change in lymphocyte locomotion.
Int J Mol Med 2001 Aug
PMID:Locomotion of lymphocytes towards melanoma cells treated with tumor necrosis factor in a syngeneic in vitro model. 1144 75

Melanoma antigen (MAGE), a tumor-associated antigen, is a product of members of a gene family that consist of 24 structurally related genes. MAGE genes are expressed only in the testis among normal tissues, but they are also expressed in a number of human tumors of various histological types. Although the MAGE expression is primarily regulated by the genome-wide demethylation of CpG dinucleotides, the demethylation of CpG dinucleotides does not always result in the MAGE expression. In the present study, we demonstrated that 40 mM NaCl induces the transcriptional and translational activation of MAGE-B1 and -B2 in specific tissues. The mRNA stability analyses revealed that the half-life of the MAGE-B1 mRNA is about 5 h. No change in the stability of the MAGE-B1 mRNA was induced by the NaCl treatment, which suggests the transcriptional activation of MAGE-B1 by NaCl. This is the first report that the MAGE expression is regulated by means other than the genome-wide demethylation of CpG dinucleotides.
Mol Cells 2002 Apr 30
PMID:Hypertonicity induction of melanoma antigen, a tumor-associated antigen. 1201 52


1 2 3 4 5 6 7 8 9 10 Next >>