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)

Activation of cellular or c-oncogenes and loss of function of suppressor genes appears to be the key event in the formation of most human cancers. Altered forms of these genes or their protein products have the potential to provide a new generation of cancer markers. As cancer markers, the most useful application of c-oncogenes and suppressor genes so far, has been in providing prognostic information. The correlation of N-myc gene amplification with poor prognosis in neuroblastoma was one of the first examples of prognostic data supplied by a c-oncogene. Most, but not all investigators, find that either amplification or increased expression of c-erbB-2 gene correlates with poor prognosis in breast cancer. Other potential prognostic markers in breast cancer include amplification of the c-myc gene, and increased expression of both EGFR and p53 protein. Although c-oncogenes and suppressor genes have the potential to supply prognostic information in a broad range of cancers, many of the results are still preliminary with conflicting conclusions.
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PMID:Cellular oncogenes and suppressor genes as prognostic markers in cancer. 812 58

Cancer has been defined as a fundamental disorder of cellular growth control. Which arises in some cells through changes in genes (DNA-level: geneamplification, mutation and rearrangement) or their expression (RNA- and protein-level), and gives these cells a growth advantage in comparison to the surrounding cells. Since the last decade we know the identity of these genes and the nature of the changes they underwent in the cancer cell. Only a few of the known oncogenes play a role in head and neck cancer. These are the EGFR (epidermal growth factor receptor), c-myc, the ras gene family, int-2, hst- 1 and bcl- 1. In some clinical disorders, like childhood neuroblastoma and breast cancer, oncogenes play already an important role in tumor staging as well as a prognostic parameter. The aim for the future is the therapeutic application of oncogenes better known as gene therapy.
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PMID:Oncogenes related to head and neck cancer. 813 94

The N-myc gene is amplified and overexpressed in neuroblastoma, retinoblastoma and small cell lung carcinoma, and is considered to be related to cell proliferation and/or differentiation. The transcriptional regulatory sequences of the c-myc gene have been already identified, while those of N-myc have remained obscure for a long time. In this report, we have identified several positive and negative transcriptional regulatory elements in the upstream region of the mouse N-myc gene. Among them, an activating sequence spanning -860 to -797 bp (63 bp) could be reduced to a functional core of 21 bp from -846 to -826. This sequence, termed N21 box, worked as a positive transcriptional element when linked directly upstream (but not downstream) of the putative N-myc promoter in HeLa, not in IMR32 cells. At least two proteins, of 42 kDa and 100 kDa, bound to the double-stranded N21 box, and were expressed in HeLa as well as in IMR32 cells. Moreover, the plus strand of N21 box could be specifically bound by a species of 42 kDa from either cell type and by a 37 kDa protein found only in HeLa cells. These proteins may be factors binding to positive transcriptional regulatory elements and may have a role in the regulation of N-myc expression.
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PMID:Transcriptional regulation of the N-myc gene: identification of positive regulatory element and its double- and single-stranded DNA binding proteins. 824 Dec 68

The cell line AG-F was isolated from the marrow of a neuroblastoma patient undergoing myeloablative treatment and autologous bone marrow rescue. A year later, the patient developed a Hodgkin's type lymphoma. AG-F cell line demonstrated an unusual phenotype, lacking surface CD2 and CD3, but expressing high levels of CD4, CD5, CD7, CD29, and CD45RO. Markers associated with Hodgkin's lymphoma cells, CD15 and CD30, were also positive. AG-F cells grow in suspension in clusters of 50-200 cells, with a doubling time of 9 h. They can also grow in serum-free medium and form tumors in nude mice. AG-F cells have amplified N-myc and c-myc and high levels of the corresponding mRNA transcripts. Cytogenetic analysis revealed a DNA index by flow cytometry of near tetraploid cells and a karyotype of 85-87 chromosomes, with consistent abnormalities in chromosomes 1, 5, and 9. Gene rearrangement studies revealed rearrangement of the beta gene of the T-cell receptor. AG-F cells secrete high levels of IL-6, IL-8, IL-10, and GM-CSF. Cell adherence and formation of long processes could be induced by fibronectin and were enhanced by exposure to PMA. Cells exposed to phorbol myristate acetate (PMA) had increased expression of CD11a, CD11b, CD18, CD45RO, and HLA-DR, whereas expression of CD15 and CD30 was markedly decreased. Similarly, the level of c-myc and N-myc oncoproteins and the levels of the cytoskeletal proteins, actin, tubulin, and vimentin markedly decreased early after PMA-induced differentiation.
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PMID:Isolation and characterization of an early T-helper/inducer cell line with a unique pattern of surface phenotype, constitutive cytokine secretion and myc oncogene expression. 825 4

Protein kinase C (PKC) is a serine/threonine kinase which is thought to play an important role in cellular proliferation and differentiation. PKC activity is stimulated physiologically by diacylglycerol and experimentally by phorbol esters. Long-term exposure of human neuroblastoma cells to phorbol esters results in down-regulation of PKC activity and induction of neuronal differentiation. In this study, we explored the hypothesis that reduced PKC expression is necessary for differentiation of the human neuroblastoma cell line SK-N-SH. PKC activity and PKC-alpha mRNA levels were assayed in cultured SK-N-SH cells over a period of several days in the presence or absence of serum. These determinants of PKC expression were compared with several known markers of neuroblastoma differentiation, including neurite outgrowth and steady-state levels of c-myc and GAP43 mRNA. We observed steady losses of PKC activity and PKC-alpha mRNA content after transfer of cells to serum-free or chemically defined media. However, morphological and biochemical differentiation of SK-N-SH cells occurred only in chemically defined medium, perhaps due to the presence of insulin. We conclude that while loss of PKC may be associated with neuroblastoma differentiation, diminished PKC alone is not sufficient to induce or support the differentiation process.
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PMID:PKC activity and PKC-alpha mRNA content are reduced in serum-derived human neuroblastoma cells without concomitant induction of differentiation. 834 86

In the human neuroblastoma cell line SH-SY5Y, insulin-like growth factors I (IGF-I) and II (IGF-II) are established mitogens, and IGF-I appears to promote SH-SY5Y neuronal differentiation. Studies show that c-myc gene product is a transcription factor associated with cell proliferation, and that c-myc messenger RNA levels decrease in differentiating SH-SY5Y neurons. Using Northern analysis we show that 24 h exposure of SH-SY5Y cells to IGF-I (3-10 nM) causes a 3- to 5-fold decrease in c-myc expression. The decrease in c-myc expression due to IGF-I is mediated via the type I IGF receptor and coincides with an IGF-I-mediated induction of the neuronal differentiation markers growth cone associated protein 43 and tissue type plasminogen activator. Under these conditions, IGF-I (10 nM) did not markedly affect the levels of Max messenger RNA expression. Thus, the differentiation promoting activity of IGF-I in SH-SY5Y cells in part due to IGF-I-dependent regulation of the expression of genes involved in neuronal differentiation.
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PMID:Insulin-like growth factor I regulates c-myc and GAP-43 messenger ribonucleic acid expression in SH-SY5Y human neuroblastoma cells. 847 53

Alcohol teratogenesis may be due, in part, to inhibition of neuronal differentiation by alcohol. Because decreases in the N-myc and c-myc proteins are believed to be linked causally to neuronal differentiation, we hypothesized that alcohol would increase N-myc and c-myc proteins in undifferentiated neuronal cells and would oppose the decreases in these two proteins that normally precede differentiation. In undifferentiated LA-N-5 cultured human neuroblastoma cells, alcohol increased N-myc protein levels (178% vs. control cells) and c-myc levels (222% of control). Retinoic acid decreased N-myc and c-myc and induced neurite outgrowth (a differentiation marker). Alcohol prevented retinoic acid-elicited decreases in both myc isoforms and prevented neurite outgrowth. A significant 100% increase in c-myc and an upward trend (48%) in N-myc were observed in CA1 pyramidal neurons of the dorsal hippocampus in mouse fetuses exposed prenatally to alcohol. These data suggest that increases in N-myc and c-myc protein levels are associated with inhibition of neurite extension by alcohol.
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PMID:Alcohol inhibits neurite extension and increases N-myc and c-myc proteins. 851 45

Estrogens are known to modulate the growth rate and differentiation state of a number of cells. In uterine, as well as in mammary tumor cells, estrogen-dependent proliferation and differentiation are correlated to a series of biochemical responses, including increased expression of proto-oncogenes such as: c-fos, c-jun and c-myc. Since estrogens were shown to regulate the proliferation and the differentiation state of cells of nervous origin, the aim of the present study was to investigate whether these effects were associated to changes in the expression of early genes. In the model system utilized, the human cell line SK-ER3, an increase in c-fos mRNA and Fos protein without change of c-jun and related genes mRNA concentration was observed after short term treatment with 17 beta-estradiol (E2). A significant decrease of c-fos, c-jun and jun-D proto-oncogene mRNA levels were found after prolonged hormonal treatment. The exposure to the hormone did not determine any change in N-myc expression. Since the three protooncogene mRNAs are rapidly induced following estrogen treatment in other cell systems and target tissues, it is concluded that the estrogen-induced differentiation of neuroblastoma cells is correlated to a pattern of expression of early genes that might be peculiar for the activity of this hormone in neural cells.
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PMID:Expression of early genes in estrogen induced phenotypic conversion of neuroblastoma cells. 874 25

1alpha,25-Dihydroxyvitamin D3 (1,25(OH)2D3) alters the proliferation of neuroblastoma cells in culture in part via a nerve growth factor (NGF)-mediated pathway. This suggests that factors other than NGF also play a role in the growth arrest induced by 1,25(OH)2D3. To more fully characterize the effect of 1,25(OH)2D3 on neuroblastoma cells, we treated the cells with 10(-8) M 1,25(OH)2D3 and examined the cells for changes in the expression of N-myc, c-myc, transforming growth factor-beta2 (TGF-beta2), and protein kinase C (PKC) activity. Our results show that 1,25(OH)2D3 causes a decrease in the expression of N-myc and c-myc, as well as a two-fold increase in total PKC activity and a dose-dependent increase in TGF-beta2 expression. These results show that 1,25(OH)2D3 regulates the expression of growth-regulatory factors other than NGF in neuroblastoma cells and that 1,25(OH)2D3 influences the growth of neural cells via multiple growth regulatory pathways.
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PMID:1,25-dihydroxyvitamin D3 regulates the expression of N-myc, c-myc, protein kinase C, and transforming growth factor-beta2 in neuroblastoma cells. 919 27

Insulin-like growth factor-I (IGF-I) induces neuronal differentiation in vitro. In the present study, we examined the signaling pathway underlying IGF-I-mediated neurite outgrowth. In SH-SY5Y human neuroblastoma cells, treatment with IGF-I induced concentration- and time-dependent tyrosine phosphorylation of the type I IGF receptor (IGF-IR) and extracellular signal-regulated protein kinases (ERK) 1 and 2. These effects of IGF-I were blocked by a neutralizing antibody against IGF-IR. Whereas IGF-IR phosphorylation was observed within 1 min, maximal phosphorylation of ERKs was not reached for 30 min. Both IGF-IR and ERK phosphorylation were maintained for at least 24 h. Also, the concentration dependence of IGF-I-stimulated IGF-IR and ERK tyrosine phosphorylation paralleled that of IGF-I-mediated neurite outgrowth. We further examined the role of mitogen-activated protein kinase activation in IGF-I-stimulated neuronal differentiation using the mitogen-activated protein kinase/ERK kinase inhibitor PD98059. Whereas PD98059 had no effect on IGF-IR phosphorylation, PD98059 reduced IGF-I-mediated ERK tyrosine phosphorylation and ERK phosphorylation of the substrate Elk-1. PD98059 also produced a parallel reduction of IGF-I-stimulated neurite outgrowth. Finally, consistent with its ability to block neuronal differentiation, PD98059 inhibited IGF-I-dependent changes of GAP-43 and c-myc gene expression. Together these results suggest that activation of ERKs is essential for IGF-I-stimulated neuronal differentiation.
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PMID:Insulin-like growth factor-I-mediated neurite outgrowth in vitro requires mitogen-activated protein kinase activation. 926 Nov 37


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