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 butenolide compound (1E,3E,5E,7E)-5-hydroxy-4-(8-phenyl-1,3,5,7- octatetraenyl)-2(5H)-furanone (KNK-41), was shown to have strong anti-tumor activity. KNK-41 inhibited the proliferation of various kinds of human malignant tumor cells, such as HeLa (cervical carcinoma), HGC-27 (gastric cancer), PANC-1 (pancreatic cancer) and GOTO (neuroblastoma). Flow cytometric analysis indicated that KNK-41 caused an arrest in G0/G1 phase of the cell cycle. However, it scarcely affected DNA synthesis and the level of c-myc mRNA. These results suggest that the growth-inhibitory effect of KNK-41 is the result of G0/G1 arrest and not of the suppression of DNA synthesis and/or c-myc expression.
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PMID:Inhibitory effects of (1E,3E,5E,7E)-5-hydroxy-4-(8-phenyl-1,3,5,7- octatetraenyl)-2(5H)-furanone on proliferation of human malignant tumor cells. 157 90

Natural carotene sample obtained from palm oil was proved to suppress the promoting stage of two-stage carcinogenesis of mouse skin, and also inhibit the proliferation of human malignant tumor cells, such as neuroblastoma GOTO cells, stomach cancer HGC-27 cells, and pancreatic cancer PANC-I cells. Among the major constituents of palm carotene, alpha-carotene showed stronger anti-proliferative effect than beta-carotene. The present results indicate that further investigation for not only beta-carotene but also other kinds of natural carotenes, such as alpha-carotene, should be carried out.
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PMID:[Anticarcinogenesis activity of natural carotenes]. 252 99

RINm5F, a rat insulin-secreting pancreatic cell line, responds to nerve growth factor (NGF) by extending neurite-like processes. Secretogranin II (SgII), a marker of neuroendocrine secretory organelles, has recently been found to be a good marker of neuronal differentiation in both human neuroblastoma and rat pheochromocytoma cells. The present paper reports the results obtained from immunocytochemical studies, which show that NGF increases the expression of SgII-immunolabeled organelles in RINm5F cells. We also demonstrate that NGF increases the expression of insulin and that SgII and insulin are predominantly, but not always, colocalized. These results suggest that this insulinoma cell line may be a good model for studying the role of SgII in neuroendocrine secretion mechanisms.
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PMID:Immunolocalization of secretogranin II and insulin in a nerve growth factor-differentiated insulinoma cell line. 764 27

3'-methyl-3-hydroxy-chalcone (3'Me-3-C), a derivative of chalcone, inhibited the proliferation of various kinds of human malignant tumor cells, such as HGC-27 (gastric cancer), HeLa (cervical carcinoma), PANC-1 (pancreatic cancer) and GOTO (neuroblastoma). Flow-cytometric analysis of HGC-27 cells revealed that 3'Me-3-C perturbed the cell cycle, i.e., it delayed passage through the S phase, and/or caused arrest in the G0/G1 phase. 3'Me-3-C inhibited the binding of [6,7-3H]estradiol to type-II estrogen-binding sites dose-dependently, and altered the pattern of protein synthesis and phosphorylation, which may explain 3'Me-3-C-induced inhibition of cell proliferation. In addition, 3'Me-3-C also suppressed the promoting activity of 12-0-tetradecanoylphorbol-13-acetate on skin carcinogenesis in 7,12-dimethylbenz[a]anthracene-initiated mice.
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PMID:Inhibitory effects of 3'-methyl-3-hydroxy-chalcone on proliferation of human malignant tumor cells and on skin carcinogenesis. 837 34

Secretogranin II is an acidic secretory protein with a widespread distribution in secretory granules of neuronal and endocrine cells. The secretogranin II gene contains, like other members of the granin family, a cAMP response element (CRE) in its upstream region. To investigate the functional significance of this motif, intracellular cAMP levels were increased in a neuronal cell line derived from the septal region of the brain and the level of secretogranin II gene expression was analysed. It was found that increased cAMP levels did, in fact, induce secretogranin II gene expression. To analyse the cis-acting sequence responsible for this induction, a hybrid gene containing the upstream region of the mouse secretogranin II gene fused to beta-globin as a reporter was constructed. Transfection analysis revealed that cAMP-induced transcription of the secretogranin II promoter/beta-globin gene in septal and insulinoma cells. DNA-protein binding assays showed that recombinant CRE-binding protein (CREB), produced in bacteria or human cells, bound in a sequence-specific manner to the secretogranin II promoter CRE. Moreover, deletion mutagenesis revealed that the CRE motif is a bifunctional genetic regulatory element in that it mediates basal as well as cAMP-stimulated transcription. Interestingly, cAMP had no effect upon secretogranin II gene transcription in PC12 and neuroblastoma cells. An increase in the intracellular cAMP concentration activated a GAL4-CREB fusion protein upon transcription in neuroblastoma cells indicating the integrity of the cAMP signaling pathway to the nucleus. Basal as well as cAMP-stimulated transcription, directed from the secretogranin II promoter was, however, impaired in insulinoma cells by overexpression of CREB-2, a negative-acting CRE-binding protein. These results indicate that competitive effects are likely to occur between CRE-bound transcriptional activators and repressors. We conclude that cAMP-stimulated induction of secretogranin II gene transcription is mediated by the CRE motif in a cell-type-specific manner, and is likely to depend on the balance between positive and negative CRE-binding proteins in a particular cell type.
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PMID:Identification of a functional cAMP response element in the secretogranin II gene. 861 62

Secretogranin II (SgII) is a member of the granin family of secretory proteins, which are selectively expressed in neuroendocrine cells. As a first step in understanding the molecular basis for cell type-specific expression of SgII, we isolated a 12-kb clone from a rat genomic library that contained the entire rat SgII coding region, the transcription initiation site, and approximately 3 kb of 5'-flanking region. Within 75 bp of the transcription start site (+1) we located a TATA box and a consensus cAMP responsive element. Within the 5'-flanking region, a number of potential cis-acting elements were identified, including 2 Pit-1 binding sites, 15 E box motifs, and near-perfect matches for AP-1 and AP-2 sites. To demonstrate cell type-specific expression the rat SgII gene, a plasmid containing 2.6 kb of the 5'-flanking region of the SgII gene fused to the luciferase reporter gene (p2774Luc) was transfected into rat pheochromocytoma PC-12 cells, rat pituitary GH4C1 (GH) cells, human BE(2)-M17 (M17) neuroblastoma cells, and mouse fibroblast NIH/3T3 cells. The promoter activity was 6- to 36-fold higher in neuroendocrine cells than in NIH/ 3T3 cells. Progressive deletions in the 5'-flanking region to 61 bp upstream of the start site (p223Luc) had no effect on promoter activity in PC-12 cells. On the other hand, a 5'-deletion in the SgII promoter to -1032 increased promoter activity 3.8-fold in GH cells. This level of expression was maintained when the SgII promoter was further truncated to -189, whereas truncation to -61 resulted in a 2.6-fold reduction in promoter activity. These results suggest that the sequence between -61 and +162 bp is sufficient for SgII promoter activity in PC-12 cells. However, other elements in the 5'-flanking region contribute to both positive and negative regulation of the rat SgII gene in GH cells.
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PMID:Cell-specific expression of the rat secretogranin II promoter. 875 52

The chromogranins are a class of acidic proteins found in large secretory granules of neuroendocrine tissues and tumors derived from them. We measured the relative amounts and characterized the molecular forms of two members of this family, i.e. chromogranin A and secretogranin II, in 14 neuroblastomas and five ganglioneuromas. In all the tumors investigated significant amounts of chromogranin A and secretogranin II were found. Neuroblastomas contained two times and ganglioneuromas 45 times more secretogranin II compared to chromogranin A. Both proteins were processed in these tumors to a great extent to smaller peptides, only limited amounts of intact chromogranin A or secretogranin II were present. In general, proteolytic processing of secretogranin II to the small neuropeptide secretoneurin was more complete than that of chromogranin A to the peptide GE-25. Proteolytic processing of both chromogranins as well as the total amounts of these proteins were unrelated to tumor staging.
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PMID:Levels and molecular forms of chromogranins in human childhood neuroblastomas and ganglioneuromas. 975 94

Polypeptide growth factors secreted from the target tissue determine the choice of transmitter synthesis in the innervating nerves. We have investigated whether they also influence the expression of chromogranins and neuropeptide Y, components co-stored with the neurotransmitters within large dense-core vesicles. IMR-32 and SH-SY5Y human neuroblastoma cells were treated for up to six days with various neurotrophic growth and differentiation factors. For chromogranins A and B, no significant changes at the mRNA level were observed and for chromogranin A this was confirmed at the protein level. The expression of secretogranin II/pro-secretoneurin mRNA, however, was considerably enhanced in both cell lines after basic fibroblast growth factor treatment. In IMR-32 cells we determined a fast and continuous induction, whereas the up-regulation in SH-SY5Y cells was more delayed. A transient elevation of secretogranin II/pro-secretoneurin mRNA levels was seen in SH-SY5Y cells in response to epidermal growth factor. In these cells we also measured the amounts of secretogranin II/pro-secretoneurin protein which were increased by both growth factors. In addition to the above described changes in secretogranin II/pro-secretoneurin biosynthesis we extended and confirmed data available on neuropeptide Y. We found a qualitatively similar pattern of biosynthesis regulation as for secretogranin II/pro-secretoneurin, indicating that the ultimately increased expression of the two proteins may be characteristic of the phenotypic differentiation after growth factor treatment. Moreover, this finding of a concomitant regulation further emphasizes the concept of secretogranin II/pro-secretoneurin being a neuropeptide precursor from which the functional peptide secretoneurin is proteolytically liberated.
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PMID:Regulation of chromogranin biosynthesis by neurotrophic growth factors in neuroblastoma cells. 1091 87

We have recently found that cells derived from human neuroblastoma, a sympathetic nervous system (SNS) tumor, dedifferentiate and acquire a neural crest-like phenotype when exposed to hypoxia. In the present study, global analysis of gene expression and quantitative PCR of relevant genes showed that hypoxia provokes a general adaptive response in neuroblastoma cells and confirm loss of the neuronal phenotype and gain of stem-cell characteristics. Of the approximately 17,000 genes and ESTs analyzed, 199 were consistently upregulated and 36 were downregulated more than 2-fold by hypoxia. As anticipated, several genes involved in glucose and iron metabolism and neovascularization were upregulated, the latter group we here show to include the gene encoding chromogranin C and its cleavage product, secretoneurin, a vascular smooth muscle cell mitogen. We also observed upregulation of genes implicated in cell survival and growth, such as vascular endothelial growth factor (VEGF), neuropilin 1, adrenomedullin, and IGF-2. Several metallothioneins, which are linked to tumor drug resistance, were upregulated, whereas the expression of MDR1 decreased. In hypoxic neuroblastoma cells, proneuronal lineage specifying transcription factors, and their dimerization partner E2-2, were downregulated, whereas their inhibitors Id2 and HES-1 were induced, providing a molecular mechanism for the hypoxia-provoked dedifferentiation of neuroblastoma cells.
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PMID:Human neuroblastoma cells exposed to hypoxia: induction of genes associated with growth, survival, and aggressive behavior. 1509 45

Identification of AP-1 target genes in apoptosis and differentiation has proved elusive. Secretogranin II (SgII) is a protein widely distributed in nervous and endocrine tissues, and abundant in neuroendocrine granules. We addressed whether SgII is regulated by AP-1, and if SgII is involved in neuronal differentiation or the cellular response to nitrosative stress. Nitric oxide (NO) upregulated sgII mRNA dependent on a cyclic AMP response element (CRE) in the sgII promoter, and NO stimulated SgII protein secretion in neuroblastoma cells. Upregulation of sgII mRNA, sgII CRE-driven gene expression and SgII protein synthesis/export were attenuated in cells transformed with dominant-negative c-Jun (TAM67), which became sensitized to NO-induced apoptosis and failed to undergo nerve growth factor-dependent neuronal differentiation. Stable transformation of TAM67 cells with sgII restored neuronal differentiation and resistance to NO. RNAi knockdown of sgII in cells expressing functional c-Jun abolished neuronal differentiation and rendered the cells sensitive to NO-induced apoptosis. Therefore, SgII represents a key AP-1-regulated protein that counteracts NO toxicity and mediates neuronal differentiation of neuroblastoma cells.
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PMID:Secretogranin II: a key AP-1-regulated protein that mediates neuronal differentiation and protection from nitric oxide-induced apoptosis of neuroblastoma cells. 1823 71


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