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

We have used cDNA subtractive cloning to identify a group of human genes that are expressed in diverse differentiated derivatives of neural crest origin but not in neuroblastoma cell lines. One of these genes was identified as CD44, which encodes an integral membrane glycoprotein that serves as the principal receptor for hyaluronate and participates in specific cell-cell and cell-extracellular matrix interactions. The repression of CD44 expression in neuroblastoma cell lines might be relevant to their high metastatic potential. We have cloned full-length cDNAs corresponding to CD44 trancscripts and identified a novel splice variant of CD44 lacking 31 amino acids of the extracellular domain. As a first step toward analysis of CD44 downregulation in neuroblastoma cells, we have mapped the CD44 RNA initiation site and analyzed the structure of the upstream regulatory region. We constructed a series of plasmids containing different amounts of CD44 upstream regulatory region linked to the bacterial chloramphenicol acetyltransferase gene and then analyzed their ability to promote transcription in neuroblastoma and melanoma cells. We found that a DNA segment including about 150 bp of the CD44 upstream region and the 5' end of the gene itself was sufficient to induce substantial transcription of the chloramphenicol acetyltransferase gene in both neuroblastoma and melanoma cells. Several upstream cis-acting elements contribute to the downregulation of CD44 in neuroblastoma cells, the most prominent being a 120-bp DNA fragment located 450 bp upstream to the RNA initiation site. Our data suggest that multiple factors might be involved in downregulation of CD44 in neuroblastoma cells.
Mol Cell Biol 1991 Nov
PMID:Expression of CD44 is repressed in neuroblastoma cells. 192 57

Bowes human melanoma cell line was investigated immunocytochemically to localize S-100 protein, HMB-45 and intermediate filament proteins. The majority of the cells showed strong positive staining with antibodies directed against S-100 protein, HMB-45 and vimentin filaments. Antibodies directed against the other cytoskeletal proteins failed to show any reactivity. These findings suggest that this transformed cell line does not dedifferentiate in culture and continues to express the specific antigens of human melanoma cells. Thus, Bowes cell line provides a useful model for studying the cellular biology and pathology of malignant melanoma.
Virchows Arch B Cell Pathol Incl Mol Pathol 1990
PMID:Bowes human melanoma cell line. An immunocytochemical study. 197 Jun 78

Moloney murine leukemia virus (MoMuLV)-induced rat T-cell lymphomas express discrete 1.8-, 2.2-, and 4-kb mRNA transcripts hybridizing under conditions of reduced stringency to a probe derived from a region upstream of the first exon of the Tpl-1/Ets-1 gene. Screening a cDNA library from one rat T-cell lymphoma with this genomic probe yielded 15 cDNA clones which were derived from 10 different genes. One of these genes, defined by the cDNA clone pRcT7a, was expressed as a 1.8-kb mRNA transcript in spleen and thymus but not in other normal rat tissues. Expression of the gene defined by the pRcT7a cDNA clone in a series of MoMuLV-induced rat T-cell lymphomas showed a perfect correlation with the expression of the rat leukocyte antigen MRC OX-44. Because of this observation, the pRcT7a clone was sequenced and it was shown to identify a gene coding for a 219-amino-acid protein. The homology between pRcT7a and the Tpl-1 probe used for its detection mapped within the 3' untranslated region of the pRcT7a cDNA clone. The pRcT7a protein, which exhibits four putative transmembrane regions and three putative glycosylation sites, contains a region which is nearly identical in sequence to a peptide derived from the rat leukocyte antigen MRC OX-44. This finding suggested that the pRcT7a cDNA clone defines the gene coding for OX-44. To confirm this finding, a pRcT7a construct in the retrovirus vector pZipNeo was introduced into the OX-44- T-cell lymphoma line 2788. Immunostaining with the MRC OX-44 monoclonal antibody followed by flow cytometry revealed that following gene transfer, the 2788 cells became OX-44+. Sequence comparisons revealed that pRcT7a/MRC OX-44 is a member of a family of genes which includes the melanoma-specific antigen ME491; the human leukocyte antigen CD37; the protein TAPA-1, which is expressed on the surface of human T cells and appears to be involved in growth regulation; the human gastrointestinal tumor antigen CO-029; and the Schistosoma mansoni-associated antigen Sm23.
Mol Cell Biol 1991 May
PMID:The rat leukocyte antigen MRC OX-44 is a member of a new family of cell surface proteins which appear to be involved in growth regulation. 201 81

Type I interferon and difluoromethylornithine have been shown to exert an antiproliferative effect, both alone and in combination, in several tumor cell lines. Using B16 melanoma cells, we have shown that these two drugs inhibit growth over 72 hr in vitro. The estimated ED50 values for difluoromethylornithine and type I interferon were 31.1 +/- 1.1 microM and 22.3 +/- 2.7 IU/ml, respectively. When used in combination, a marked synergism was observed, as detected by isobologram analysis. Type I interferon, at concentrations that exhibited synergistic activity with difluoromethylornithine, did not affect ornithine decarboxylase activity or intracellular polyamine concentrations. These data suggest that the synergistic antiproliferative effect of murine type I interferon in combination with difluoromethylornithine is not mediated via polyamine depletion. When we examined the type I interferon receptor numbers on the B16 cells exposed to 5 IU/ml murine type I interferon for 72 hr, a 40% decrease was observed, compared with that seen in control cells. Difluoromethylornithine, at 10 microM, did not affect type I interferon receptor numbers. However, when added to the cells in the presence of murine type I interferon, difluoromethylornithine completely inhibited down-regulation, suggesting that down-regulation of the type I interferon receptor is a polyamine-dependent process. These observations may provide a basis for enhancing the therapeutic efficacy of interferon treatment through control of interferon receptor down-regulation.
Mol Pharmacol 1990 Oct
PMID:Difluoromethylornithine prevents the down-regulation of type I interferon receptors: a possible mechanism for a synergistic antiproliferative effect. 214 87

The thymidine analog 5-bromodeoxyuridine (BrdU) suppresses pigmentation and tyrosinase activity in Syrian hamster melanoma cells W1-1-1. Studies on the molecular mechanism of suppression of pigmentation indicated that BrdU treatment affects the level of tyrosinase gene transcripts. No detectable tyrosinase message was found by Northern blot analysis in cells cultured in the presence of BrdU at concentrations even as low as 0.2 microM. The level of tyrosinase mRNA was found to reflect the level of pigmentation and tyrosinase activity. Studies with dibutyryl cyclic AMP (cAMP) showed that it inhibited pigment synthesis in W1-1-1 cells. With increasing concentrations of cAMP ranging from 10 microM to 300 microM, pigmentation and tyrosinase activity decreased progressively. This inhibition was found to be associated with a corresponding decrease in the level of tyrosinase mRNA. W1-1-1 cells were found not to respond to melanocyte stimulating hormone (MSH). There was no change in pigmentation, tyrosinase activity, or tyrosinase mRNA level in W1-1-1 cells in the presence of MSH. Similarly, theophylline, a phosphodiesterase inhibitor, had no effect on pigmentation or tyrosinase activity in W1-1-1 cells.
Somat Cell Mol Genet 1990 Nov
PMID:Bromodeoxyuridine- and cyclic AMP-mediated regulation of tyrosinase in Syrian hamster melanoma cells. 217 54

Retinoids inhibit the growth and enhance the differentiation of murine S91-C2 melanoma cells. Specific alterations in gene expression are a plausible mechanism for these effects. Since nuclear retinoic acid receptors (RAR) are likely mediators of retinoid-induced changes in gene expression, we used Northern blotting to analyze the expression of RAR alpha, RAR beta, and RAR gamma in S91-C2 cells. mRNA for both RAR alpha and RAR gamma was detected in these cells, but no RAR beta mRNA could be found. Treatment with 10(-7) and 10(-6) M beta-all-trans-retinoic acid (RA) for 24 h caused a 1.5- to 2-fold increase in RAR alpha and RAR gamma mRNA, whereas lower concentrations of RA were ineffective. RAR beta mRNA, which was undetectable in untreated cells, was detected after 24 h of treatment with a RA concentration as low as 10(-9) M, and its level increased with up to 10(-6) M RA. At the latter dose, RAR beta mRNA induction occurred by 4 h and increased progressively, reaching a plateau after 24 h of treatment. RAR beta mRNA induction at 4 h was not inhibited by cycloheximide at a concentration that suppressed protein synthesis by more than 90%. Several retinoids and related synthetic compounds, including 13-cis RA, TTNPB, Ch55, Am80, and the trifluoromethyl nonyloxyphenyl analog of RA, also induced RAR beta mRNA, whereas a 24-h treatment with 10(-6) M retinol, TTNP (a decarboxylated analog of TTNPB), or the phenyl analog of RA failed to induce RAR beta mRNA. With the exception of retinol and the trifluoromethyl nonyloxyphenyl analog of RA, the ability of the retinoids to induce RAR beta mRNA and their growth inhibitory effect were correlated. However, S91-C154, a RA-resistant mutant subclone derived from S91-C2 cells, showed mRNA levels of RAR alpha and RAR gamma and induction of RAR beta by RA similar to those detected in the sensitive S91-C2 cells. Like the S91 melanoma cells, two other mouse melanoma cell lines, K-1735P and B16-F1, constitutively expressed RAR alpha and RAR gamma mRNAs. The level of RAR beta mRNA was increased by RA only in B16-F1 cells, although the growth of both was inhibited by RA. These results demonstrate that RA can, directly and rapidly, induce the expression of mRNA for a high affinity nuclear receptor in some murine melanoma cells and that this induction is not sufficient to inhibit growth.
Mol Endocrinol 1990 Oct
PMID:Modulation by retinoids of mRNA levels for nuclear retinoic acid receptors in murine melanoma cells. 217 20

We investigated Plasmodium falciparum parasitized erythrocyte binding to proteolytic fragments of thrombospondin and the effects of anti-thrombospondin monoclonal antibodies on this binding. Purified human platelet thrombospondin was cleaved by trypsin, chymotrypsin or thrombin. Fragments were separated by heparin-agarose affinity chromatography, removing the amino-terminal heparin-binding region. Trypsin at 5.0 micrograms ml-1 of thrombospondin cleaved thrombospondin to reduced 140 and 120 kDa fragments plus a reduced 25-kDa heparin-binding fragment. Infected erythrocytes bound to intact thrombospondin (3420 +/- 460 infected erythrocytes mm-2) and the carboxy-terminal fragment, yielding 120-140-kDa fragments on sulfhydryl reduction, but not to the 25-kDa fragment (144 +/- 104 infected erythrocytes mm-2 (mean +/- s.d., N = 4). Similar results were obtained with chymotrypsin and thrombin cleavage. When the anti-thrombospondin monoclonal antibody MA-I was added to immobilized thrombospondin prior to infected erythrocytes, adherence was inhibited by 99%. At the same concentration, MA-I inhibited adherence to C32 melanoma cells by only 35%. MA-I binds to a calcium-dependent structure at the C-terminal globular region of thrombospondin. Monoclonal antibody MA-II inhibited adherence to thrombospondin by 46%, while MA-III had no effect. These antibodies bind to the N-terminal globular region which includes the heparin-binding site and the segment connecting the two globular regions, respectively. The site(s) for infected erythrocyte binding on thrombospondin reside in the large, 140- or 120-kDa, proteolytic cleavage fragments, and not in the N-terminal heparin-binding region.
Mol Biochem Parasitol 1990 May
PMID:Falciparum malaria parasitized erythrocytes bind to a carboxy-terminal thrombospondin fragment and not the amino-terminal heparin-binding region. 219 22

Analysis of different cellular fractions after incubation of SW 948 and SW 707 colorectal carcinoma cells or WM 266-4 melanoma cells with 125I-insulin revealed the nondegraded hormone in the chromatin of these cells. Nuclear 125I-insulin was bound to specific fragments of EcoRI-, HaeIII-, and HincII-digested chromatin. A 45-kDa chromatin protein species that binds 125I-insulin was identified. Actinomycin D and cycloheximide inhibited the insulin-stimulated expression of chromatin receptors. Uptake of 125I-insulin by isolated nuclei occurred only in the presence of plasma membranes. Thus, at least some effects of insulin on target cells can be explained by direct gene regulation instead of "second messenger" action.
Mol Carcinog 1990
PMID:Plasma membrane-mediated nuclear uptake and chromatin binding of insulin in tumor cell lines. 219 1

The p85 glycoprotein expressed on a variety of human cell types including astrocytes and lymphocytes has not been associated with the CD44 cluster. The recent demonstration that Hermes, a glycoprotein implicated in the adhesion of lymphocytes to endothelium, belongs to the CD44 cluster raises interesting questions concerning the role of this molecule on astrocytes and on non-lymphoid cells. To obtain confirmation of the identity of p85 glycoprotein and CD44, p85 glycoprotein was purified from B-chronic lymphocytic leukemia cells by affinity to monolonal 50B4-IgG and electrophoretic elution, digested with trypsin or CNBr and fractionated by reversed-phase HPLC. The sequences of three peptides were obtained which could be aligned with the amino acid sequence deduced from the CD44 cDNA at residues 49-54, 59-66 and 309-323. These constitute the first reported peptide sequences for antigens of the CD44 cluster and confirm that p85 glycoprotein is indeed the product of the CD44 gene. Since two different cDNA clones encoding molecules with cytoplasmic tails of 72 and 5 amino acids have been isolated, the isolation of peptide 309-323 confirms the existence of a processed protein with the longer cytoplasmic domain. Using a cDNA probe, we have characterized the expression of CD44 in several normal and malignant cell types. The level of CD44 mRNA was correlated with the surface expression of CD44 antigens (50B4) in several leukemic cell lines, in astrocytoma lines and in normal granulocytes. Negative cells included the Y79 retinoblastoma line, the NALM-6 leukemic line and endothelial cells. Identical mRNA species of 5.0, 2.3 and 1.7 kb were present in all CD44-positive samples, including normal granulocytes, astrocytoma, melanoma and leukemia cell lines and leukemic cells from patients. The highest level of expression of CD44 was observed on astrocytoma lines and on acute lymphoblastic leukemia cells of immature phenotype. The presence of high levels of CD44 on malignant cells could increase the ability of these cells to adhere to matrix proteins and/or to interact with endothelium, thus potentially altering their capacity for invasiveness and metastasis.
Mol Immunol 1990 Oct
PMID:Confirmation by peptide sequence and co-expression on various cell types of the identity of CD44 and P85 glycoprotein. 223 56

Metallothioneins (MTs) protect cells from the toxic effects of heavy metals. It has been suggested that they play a role in cellular resistance to alkylating agents and ionizing radiation because of the coincidence of cadmium- and drug-resistance and by virtue of the reactivity of MT with free radicals. We report the analysis of mouse B16 melanoma cell lines with high and low constitutive MT expression. In these cells, both cisplatin and cadmium resistance were associated with constitutive MT accumulation in the absence of heavy-metal induction. However, in cells with high constitutive MT expression (where zinc treatment did not induce increased MT expression), cisplatin resistance, but not cadmium resistance, was increased approximately twofold by zinc treatment. Methotrexate resistance also was increased by zinc treatment in some cases. We conclude that MT is associated with cisplatin resistance, but that effects of heavy-metal treatment other than MT induction are also responsible for cisplatin and methotrexate, but not cadmium, resistance.
Somat Cell Mol Genet 1990 Nov
PMID:Zinc treatment, metallothionein expression, and resistance to cisplatin in mouse melanoma cells. 226 27


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