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)

In this report we provide evidence for the activation of distinct differentiation pathways during treatment of the neuroblastoma cell line SMS-KCNR with 1 mM dibutyryl cyclic AMP (dbcAMP) and/or 5 microM retinoic acid (RA). Our results show that the adrenal gland specific gene pG2 is induced only during dbcAMP treatment, while RA induces a neuronal phenotype and expression of all neural related genes while decreasing the expression of many chromaffin related genes. Furthermore dbcAMP does not affect the DNA content distribution of SMS-KCNR [G1 = 61.8 +/- 4.1% (SD); S = 20.3 +/- 6.3%; G2-M = 18 +/- 5.4%] despite morphological and molecular signs of cellular differentiation. Conversely, RA arrests cell growth causing a decrease in cells in the growth fraction (S + G2 + M = 15.6 +/- 6.1%) and an increase in cells in G1 (G1 = 84.3 +/- 5%). Using cyclic AMP and RA in combination, we found that RA inhibited expression of adrenal gland specific gene pG2 and induced a neuronal phenotype. Since dbcAMP does not cause a significant G1 block in SMS-KCNR cells we propose that this agent may be able to induce SMS-KCNR only to an intermediate stage of chromaffin differentiation in which cells retain their proliferative potential.
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PMID:In vitro activation of distinct molecular and cellular phenotypes after induction of differentiation in a human neuroblastoma cell line. 132 87

The expression and structure of the receptors for neuropeptide-Y (NPY) and peptide-YY (PYY) were studied in 16 human and rodent tumor cell lines derived from the neural crest by ligand binding and cross-linking techniques using [125I]Bolton-Hunter-NPY, [125I]PYY, and various forms of monoiodinated NPY and PYY. Although NPY-binding sites were observed in most of the tumor cells, PYY-binding sites were found only on the human neuroblastoma cell lines SMS-MSN, SMS-KAN, SK-N-MC, and MC-IXC and the human Ewing's sarcoma cell line SK-ES. The differential labeling of the NPY/PYY receptors on these cell lines suggests that the NPY/PYY receptors are more heterogeneous than previously described as the Y1, Y2, and Y3 receptor subtypes. Cross-linking studies demonstrate that the Y1 and Y2 receptors for NPY/PYY are structurally different (mol wt, 70 and 50 kilodaltons, respectively) and that the 70- and 50-kilodalton receptor proteins are coexpressed in certain tumor cell lines. This could explain at least in part why cell lines show a relative specificity for Y1/Y2 classification, observed as the inhibition by both C-terminal fragments and Y1-specific analogs on the NPY/PYY binding to membrane receptors. Collectively, the present study suggests further heterogeneity of the NPY/PYY receptors and the existence of multiple receptor proteins in the tumor cell lines derived from the neural crest.
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PMID:Evidence for further heterogeneity of the receptors for neuropeptide-Y and peptide-YY in tumor cell lines derived from neural crest. 133 Apr 89

Human neuroblastoma (NB) cell lines have been suggested to represent a model of neural crest differentiation. The expression of several Schwann-cell-associated antigens was examined by flow cytometry and Northern blot analysis. Variable reactivity of the human NB cell lines was found in both the level and pattern of reactivity. Retinoic acid treatment of cell line SMS-KAN resulted in a neuron-like morphological differentiation and a decrease in several of the glial markers under study. Similarly, Northern blot analysis illustrated myelin-associated glycoprotein expression, and decreased expression of this message with retinoic acid treatment was consistent with the neuron-like morphological changes. Overall, human NB in vitro was found to be multipotential, but we have shown that it is capable of expressing several Schwann cell markers which are modulated during induced differentiation.
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PMID:Molecular evidence for the expression of Schwann cell markers in human neuroblastoma. 137 87

Oncogene amplification is observed frequently in human cancers, but little is known about the mechanism of gene amplification or the structure of amplified DNA in tumor cells. We have studied the N-myc amplified domain from a representative neuroblastoma cell line, SMS-KAN, and compared the map of the amplicon in this cell line with that seen in normal DNA. The SMS-KAN cell line DNA was cloned into yeast artificial chromosomes (YACs), and clones were identified by screening the YAC library with amplified DNA probes that were obtained previously (B. Zehnbauer, D. Small, G. M. Brodeur, R. Seeger, and B. Vogelstein, Mol. Cell. Biol. 8:522-530, 1988). In addition, YAC clones corresponding to the normal N-myc locus on chromosome 2 were obtained by screening two normal human YAC libraries with these probes, and the restriction maps of the two sets of overlapping YACs were compared. Our results suggest that the amplified domain in this cell line is a approximately 1.2-Mb circular molecule with a head-to-tail configuration, and the physical map of the normal N-myc locus generally is conserved in the amplicon. These results provide a physical map of the amplified domain of a neuroblastoma cell line that has de novo amplification of an oncogene. The head-to-tail organization, the general conservation of the normal physical map in the amplicon, and the extrachromosomal location of the amplified DNA are most consistent with the episome formation-plus-segregation mechanism of gene amplification in these tumors.
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PMID:Isolation and structural analysis of a 1.2-megabase N-myc amplicon from a human neuroblastoma. 144 86

Immunocytochemical, immunoblotting and in situ hybridization studies were used to map the distribution of SNAP-25 protein and mRNA in the rodent nervous system. These experiments demonstrated that subsets of neurons expressed SNAP-25, and that several patterns of expression emerged: SNAP-25 expression in caudate nucleus was initially concentrated in axons, which subsequently was localized in presynaptic regions of these axons. Other regions, typified by neocortex, showed developmental increases and persistent adult neuronal immunoreactivity for SNAP-25. Finally, olfactory bulb contained neurons which initially expressed SNAP-25, but lost expression during maturation. Additional studies in cultured human and rat cell lines derived from neural crest suggested that SNAP-25 is expressed in such lines, but not in glial or fibroblast lines. Differentiation of rat PC-12 cells with nerve growth factor failed to alter steady-state levels of SNAP-25 protein; similar responses were seen in human SMS-KCNR neuroblastoma cells differentiated using retinoic acid. The presence of SNAP-25 in presynaptic regions of numerous neuronal subsets and in neural crest cell lines suggests that this protein subserves an important function in neuronal tissues.
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PMID:Distribution and expression of SNAP-25 immunoreactivity in rat brain, rat PC-12 cells and human SMS-KCNR neuroblastoma cells. 157 61

A comparable pattern of morphological neuronal differentiation was induced in the human neuroblastoma cell line SMS-KCNR by treatment with either retinoic acid (RA) or exogenous laminin (LM). LM expression and synthesis by SMS-KCNR was increased upon RA treatment which involved the cell bound, rather than the secreted protein. These data suggest an involvement of LM in the neuroblastoma differentiation process manifested both as an ability of LM to induce a morphological neuronal differentiation and as a selective control on LM metabolism during RA induced neuronal differentiation.
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PMID:Modulation of laminin synthesis in human neuroblastoma cells during retinoic acid induced differentiation. 159 74

The interaction of helix-loop-helix (HLH) proteins is known to regulate the differentiation of several different tissues, including mammalian muscle and the insect peripheral nervous system. In myoblasts, the products of myogenic HLH genes such as MyoD and ubiquitous HLH proteins such as E12 are present at constant levels throughout development. An E12 monomer and a MyoD monomer form a DNA binding heterodimer that activates muscle-specific genes. These two proteins are unable to dimerize in proliferating myoblasts because a negative regulator HLH protein, Id, is present. We now report the sequence and structure of a human HLH gene related to Id, which has been designated Id-2. Two prominent Id-2 RNA molecules of 2.5 and 1.3 kilobases were found in a number of different human normal and neoplastic tissues. We believe the larger RNA is a precursor of the 1.3-kilobase mRNA that encodes an Id-2 protein of 134 amino acids. The HLH region of the Id-2 protein is 90% homologous to that of myogenic Id, but the homology is much less extensive outside the HLH region. The Id-2 gene is highly expressed during early fetal development in several tissues, including those of the central nervous system, but is not expressed in the corresponding mature tissues. Id-2 expression is modulated in association with retinoic acid-induced ganglionic differentiation of the neuroblastoma cell line SMS-KCNR. These findings suggest that Id-2 is an inhibitor of tissue-specific gene expression, although its distinctive pattern of expression during development suggests a role different from that of Id.
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PMID:A human Id-like helix-loop-helix protein expressed during early development. 174 6

The neural crest gives rise to a variety of tissues, including peripheral neurons, Schwann cells, melanocytes and ectomesenchymal cells, which include the smooth muscle cells of large arteries. Cell lines derived from neuroblastoma (a neural crest tumor) have at least two distinct morphological cell types, a neuroblastic phenotype (N-type) and an epithelial-like phenotype (S-type) with characteristics of substrate-adhesiveness. We have analyzed 17 human neuroblastoma cell lines using a panel of monoclonal antibodies against cytoskeletal proteins. Three neuroblastoma cell lines (KP-N-SI, KP-N-YN and SMS-KCN) bound an alpha -smooth muscle actin antibody. In addition, one of these cell lines (KP-N-SI) bound anti-desmin monoclonal antibodies as determined by indirect immunofluorescence. A total of eight cloned cell lines were obtained from the above parent cell lines. These were composed of either N- or S-type cells and were confirmed to be the common neuroblastoma origin from each parent cell line by chromosomal analysis. Alpha-smooth muscle actin and desmin were demonstrated in the S-type cloned cells by indirect immunofluorescence, as well as by two-dimensional Western blot analysis. These results were confirmed by Northern blot analysis using a specific probe (pSH alpha SMA-3'UT) to human alpha-smooth muscle actin mRNA. This is the first report of the presence of alpha-smooth muscle actin and desmin in neuroblastoma cell lines. These data show that in addition to giving rise to cells with neural, Schwann cell and melanocyte markers, neuroblastoma can also give rise to the cells expressing smooth muscle cell markers.
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PMID:[Human neuroblastoma cell lines having smooth muscle cell markers]. 178 84

The neural crest gives rise to a variety of tissues, including peripheral neurons, Schwann cells, melanocytes and ectomesenchymal cells, which include the smooth-muscle cells of large arteries. Cell lines derived from neuroblastoma (a neural-crest tumor) exhibit at least 2 distinct morphological cell types, a neuroblastic phenotype (N-type) and an epithelial-like phenotype (S-type) with characteristics of substrate-adhesiveness. We have analyzed 17 human neuroblastoma cell lines using a panel of monoclonal antibodies (MAbs) against cytoskeletal proteins. Three neuroblastoma cell lines (KP-N-SI, KP-N-YN and SMS-KCN) bound an alpha-smooth-muscle actin antibody. In addition, one of these lines (KP-N-SI) bound anti-desmin MAbs as determined by indirect immunofluorescence. A total of 8 cloned cell lines were obtained from the above parent cell lines. These were composed of either N- or S-type cells and were confirmed to have the same neuroblastoma origin as each parent cell line by chromosomal analysis. Alpha-smooth-muscle actin and desmin were demonstrated in the S-type cloned cells by indirect immunofluorescence, as well as by 2-dimensional Western blot analysis. These results were confirmed by Northern blot analysis using a specific probe (pSH alpha SMA-3' UT) to human alpha-smooth-muscle actin mRNA. These ascertain the presence of alpha-smooth-muscle actin and desmin in neuroblastoma cell lines. These data show that, in addition to giving rise to cells with neural, Schwann-cell and melanocyte markers, neuroblastoma can also give rise to the cells expressing smooth-muscle cell markers.
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PMID:Alpha-smooth-muscle actin and desmin expressions in human neuroblastoma cell lines. 201 70

We have recently identified and cloned the gene for a cytosolic polypeptide, designated oncoprotein 18 (Op18), which is expressed in acute lymphocytic leukemia and some solid tumors including neuroblastoma. Op18 is phosphorylated upon treatment of lymphoid cells with phorbol myristate acetate. We have proposed that unphosphorylated Op18 plays a role in cellular proliferation, and that its phosphorylated forms, namely Op18a and Op18b, are associated with diminished cell proliferation. In this study, we report that in neuroblastoma tumors, the phosphorylation of Op18 was substantially diminished with increasing N-myc gene copy number. Treatment of the neuroblastoma cell line SMS-KCNR, which contains 75 copies of the N-myc gene, with retinoic acid for ten days resulted in an increase in Op18 phosphorylation. Our findings provide evidence for distinct patterns of Op18 phosphorylation in neuroblastoma tumors with and without N-myc gene amplification.
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PMID:N-myc gene amplification in neuroblastoma is associated with altered phosphorylation of a proliferation related polypeptide (Op18). 226 30


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