Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A quantitative estimate of the cellular tubulin concentration can be obtained by the use of a radioimmunoassay based upon the competition between tubulin in cell extracts and a known amount of radioactively labeled homogeneous tubulin during binding to a limited amount of anti-tubulin antibodies. This assay shows that a variety of widely used tissue culture cells (mouse L cells, mouse 3T3 cells, chick embryo fibroblasts) have a tubulin content which corresponds to approximately 2.5--3.3% of their total protein. Transformation of mouse 3T3 cells by the DNA virus SV40, and of chick embryo cells by the RNA Rous sarcoma virus, does not change the intracellular tubulin concentration. Transformed cells of brain origin, such as some glia tumor cell lines and some neuroblastoma cell lines, have a much lower tubulin content than does normal brain tissue. The intracellular concentration of tubulin in mouse 3T3 cells is discussed in relation to the number of microtubules detected during interphase by immunofluorescence microscopy. These results are also discussed in view of a mechanism of microtubule elongation in vivo driven by self-assembly.
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PMID:Radioimmunoassay for tubulin: a quantitative comparison of the tubulin content of different established tissue culture cells and tissues. 68 94

Several tumor lines of neuronal origin were assayed for the presence of two forms of pp60c-src, designated pp60 and pp60+. To determine the specific kinase activity of pp60 and pp60+, an enzymatic analysis was carried out with neuroblastoma LA-N-5, containing a high level of pp60+, neuroblastoma SK-N-SH, containing a low level of pp60+, fibroblast FSD, containing pp60 but no pp60+, and Rous sarcoma virus transformed 3T3 cells, SR-3T3, containing pp60v-src. Km values for Mg2+-ATP of approximately 21, 8, 17 and 13 microM were determined for pp60src kinase from LA-N-5, SK-N-SH, FSD and SR-3T3 respectively, using enolase as a substrate. The Vmax values for pp60c-src kinase from LA-N-5, SK-N-SH and FSD were similar. The Vmax value of pp60v-src was about 50-fold higher. Thirteen distinct phosphopeptides were found in tryptic digests from pp60 and pp60+ labeled in vivo with [32P]. The presence of one phosphopeptide, derived from the N-terminus, correlated with the level of pp60+ in neuroblastoma cells, but a small amount of this peptide was also detected in fibroblasts. Only phosphoserine was detected in the N-terminus of pp60 and pp60+. Our data strongly suggest that the six extra amino acids, present in pp60+ but not in pp60, do not significantly alter the specific kinase activity of pp60+, but might influence its phosphorylation state.
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PMID:Specific kinase activity and phosphorylation state of pp60c-src from neuroblastomas and fibroblasts. 246 4

Human cell lines with neuronal and neuroendocrine features were examined for their expression of pp60c-src, the cellular homolog of the transforming gene product pp60v-src of Rous sarcoma virus. Four neuroblastoma (LA-N-5, SH-SY5Y, Paju, and SK-N-MC) and three small-cell lung carcinoma (U-2020, U-1690, and U-1285) cell lines were selected on the basis of their stage of neurocrine differentiation, as determined by the expression of neuron-specific enolase. In an immune complex protein kinase assay, all seven cell lines displayed c-src kinase activity which was considerably higher than that found in nonneurocrine cells (human diploid fibroblasts, glioma, and non-small cell lung carcinoma cell lines). Furthermore, the c-src kinase activity, as determined by autophosphorylation or phosphorylation of an exogenous substrate, enolase, correlated with the stage of neurocrine differentiation. There was an approximately 30-fold difference in c-src kinase autophosphorylation activity between the cell lines representing the highest and lowest stages of neurocrine differentiation. A similar variation was found in the steady-state levels of the c-src protein of these cell lines. Highly differentiated neuroblastoma cells expressed two forms of the src protein. Digestion by Staphylococcus aureus V8 protease did reveal structural diversity in the amino-terminal ends of these c-src molecules. In summary, we found a clear correlation between c-src kinase activity and the stage of neuronal and neuroendocrine differentiation. Thus, the phenotypic similarity between neurons and neuroendocrine cells includes high c-src expression.
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PMID:Expression of c-src in cultured human neuroblastoma and small-cell lung carcinoma cell lines correlates with neurocrine differentiation. 283 Apr 84

Incubations in vitro of GA1, labeled with 3H in the terminal D-galactopyranosyl group, with nonradioactive CMP-NeuNAc in the presence of homogenates of C21 rat brain glial cells, NIE mouse neuroblastoma cells, 3T3 mouse fibroblasts, SV 40-transformed 3T3 cells, chick embryo fibroblasts, Rous sarcoma virus-transformed chick embryo fibroblasts, and 9-day old rat brain resulted in all cases in the formation in high yield of GM1b, in which the neuraminidase-labile NeuNAc group is linked at O-3 of the terminal D-galactosyl residue, as shown by permethylation studies. No trace of the naturally occurring neuraminidase-stable GM1a was detected in any case. In addition, with NIE cells, and normal and RSV-transformed chick embryo fibroblasts, a disialosylganglioside (GD1) differing from GD1a and GD1b, and bearing only one substituent at O-3 of the terminal D-galactopyranosyl residue was formed. It was also biosynthesized from GM1b and CMP-NeuNAc by NIE and chick embryo cells but not by C21 cells, or rat brain. However, C21 cells and rat brain were capable of synthesizing GD1a from GM1a. Periodate oxidation degraded both NeuNAc groups in GD1 to a 7-carbon fragm:nt, indicating lack of substitution at O-8. GM1b could not be detected as a natural product in rat brain.
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PMID:Biosynthesis in vitro of mono- and di-sialosylgangliosides from gangliotetraosylceramide by cultured cell lines and young rat brain. Structure of the products, and activity and specificity of sialosyltransferase. 624 13

Monoclonal antibodies raised against B 16 melanoma cells in syngeneic mice were functionally screened for their ability to inhibit cell adhesion in tissue culture. Three of these antibodies (16/43, 16/77, 16/82), when preinjected into C57BL/6 mice, markedly reduced the number of experimental lung metastases produced by B 16 cells, possibly by interference with their adhesion to the lung endothelia. We now report that these monoclonal antibodies block in vitro attachment of the majority of human melanoma cell lines tested and also of carcinoma, neuroblastoma, and glioblastoma cells from both mice and humans but untransformed cell lines such as 3T3 mouse or MRC-5 human fibroblasts are not affected. The antibodies also react with mouse teratocarcinoma stem cells (F9, PCC4) but not with differentiated teratocarcinoma lines (PYS-2, 944). Furthermore, the antiadhesion activity of the antibodies could be quantitatively absorbed by intact human and mouse tumor cells but not by untransformed cells, suggesting that the corresponding antigens may represent tumor-associated cell surface components. Correspondingly, the antigens were found on simian virus 40-transformed 3T3 mouse fibroblasts and are expressed in a temperature-sensitive fashion in chicken fibroblasts transformed with a temperature-sensitive Rous sarcoma virus. On "immunoblots" of NaDodSO4-containing gels the three selected antibodies (16/43, 16/82, 19/1) were absorbed by antigens with molecular weights of 40,000 and 50,000.
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PMID:Monoclonal antibodies that prevent adhesion of B 16 melanoma cells and reduce metastases in mice: crossreaction with human tumor cells. 631 31

Different portions of the 5'-upstream region of the mouse proliferating cell-nuclear-antigen (PCNA) gene were combined with the bacterial chloramphenicol acetyltransferase (CAT) gene of a CAT vector. A transient expression assay of CAT activity in mouse neuroblastoma N18TG2 cells transfected with these recombinant plasmids and RNase protection analysis have revealed the existence of a negative regulatory region between nucleotides -1231 and -624 (+1 denotes the transcription initiation site). The CAT expression levels were gradually increased, depending on the extent of deletion from the 5'-terminus in this region, suggesting that the negative regulatory region consists of multiple elements with rather weak repressing activities. Significant sequence similarity was found between the negative regulatory region of the PCNA gene and those of the several reported genes. A 752-bp segment containing this negative regulatory region repressed the function of the PCNA gene promoter in an orientation-independent and position-independent manner. However, the negative regulatory region showed almost no repressing effect on the functions of the heterologous gene promoters such as the simian virus 40 enhancer promoter, the enhancer promoter in the Rous sarcoma virus long-terminal repeat and the mouse DNA polymerase beta gene promoter. These results suggest that the negative regulatory region of the mouse PCNA gene functions specifically to its own promoter. This unique property is discussed in comparison with that of the negative regulatory elements of the mouse DNA polymerase beta gene.
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PMID:Nucleotide sequence and promoter-specific effect of a negative regulatory region located upstream of the mouse proliferating cell nuclear antigen gene. 790 77

In PC12 cells, NGF and other ligands of tyrosine kinase receptors increased the activity of the Rous sarcoma virus (RSV) promoter. IGF-1 stimulated the RSV promoter in SH-SY5Y neuroblastoma cells. This promoter was also activated by oncogenic Ras and Raf in different cell types, and growth factor induction was inhibited by expression of dominant negative forms of ras and raf, showing that its effect is mediated by a Ras- and Raf-dependent mechanism. Therefore, the RSV promoter should not be used in the determination of transfection efficiency in the studies on regulation of gene expression by ligands of tyrosine kinase receptors, ras and raf.
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PMID:Growth factor ligands of tyrosine kinase receptors activate the Rous sarcoma virus promoter by a Ras- and Raf-dependent mechanism. 913 5

DAN gene has been isolated by means of differential screening method between rat fibroblast 3Y1 and Rous sarcoma virus-transformed 3Y1 (SR-Y1) cells. DAN expression was suppressed in some of the transformed cells and its re-expression reverted the various transformed phenotypes such as colony formation in soft agar and tumor formation in mice. When DAN was overexpressed in 3Y1 cells, these cell showed the retardation of the entry into the S phase. DAN cDNA encodes a 27-kD protein which consists of 178 amino acids. The deduced amino acid sequence has no homology with known proteins. The amino terminal of DAN is highly hydrophobic and DAN is indeed secreted into the culture medium. This secreted DAN, when added to the culture of SR-3Y1 cells, suppressed DNA synthesis. Human DAN is mapped to 1p36.11-p36.13, a region known to have highly significant linkage with the genesis and/or progression of human neuroblastoma. Aberrant bands on Southern blot were detected in some of the neuroblastoma cases. Rat and human genomic DANs were isolated. CAT and the electrophoretic mobility shift assays revealed the presence of possible positive and negative regulatory elements at -57 approximately +118 and -1,232 approximately -987 of rat genome, respectively.
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PMID:[DAN gene]. 930 43

Our previous studies have shown that the DAN gene product possesses an ability to revert phenotypes of transformed rat fibroblasts and represents a candidate tumour suppressor gene for neuroblastoma. In the present study, characterisation of DAN was carried out using rat fibroblast 3Y1 cells and their DAN-overexpressor counterparts (S-9). The N-terminal region of DAN (amino acids 1-24) was highly hydrophobic and DAN protein was found to be secreted into the culture medium. When DAN was treated with PNGase F, a enzyme that cleaves most N-linked carbohydrate residues, the mobility of both cytoplasmic and secreted DAN was increased in SDS-polyacrylamide gel electrophoresis, suggesting DAN is N-glycosylated, irrespective of its localisation. When partially purified, DAN was able, when added to the culture, to suppress DNA synthesis of Rous sarcoma virus-transformed 3Y1 cells, which lack the expression of DAN.
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PMID:A product of DAN, a novel candidate tumour suppressor gene, is secreted into culture medium and suppresses DNA synthesis. 951 39