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)

Gene amplification is a model of proto-oncogene alterations occasionally observed in human tumors. This amplification can, in some cases, have prognostic value (N-myc in neuroblastoma, c-erbB2 and int-2 in breast cancer, etc.). Amplifications of the proto-oncogenes c-myc, c-erbB2 and int-2 have not yet been report in prostate adenocarcinoma, which, like breast cancer, is hormone dependent. We sought amplifications of these three proto-oncogenes by means of Southern blotting in 15 human prostate adenocarcinoma specimens, most of which were advanced (7 stage C and 6 stage D1 or D2). We confirmed the lack of c-myc and c-erbB2 amplification, regardless of the stage, in contrast to the case of breast cancer. Int-2 amplification was observed in one advanced tumor with bone metastases, out of a total of six stage D tumors. The precise frequency of int-2 amplification and its role in prostate carcinogenesis remain to be determined.
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PMID:Gene amplifications in advanced-stage human prostate cancer. 774 Jun 53

We have investigated the relationship between the expression of bcl-2 and myc family genes in primary human neuroblastoma (NB) tumors and cell lines. Of 20 NB tumors examined, bcl-2 transcripts were expressed at variable levels in 16 tumors of all clinical stages. Of the 2 tumors with N-myc amplification, one expressed bcl-2 at a high level, whereas the other did so at a low level. In contrast, all NB tumors showed the expression of c-myc and/or N-myc transcripts. Similarly, of 9 NB cell lines with N-myc amplification examined, 6 expressed bcl-2 at high levels, whereas the other 3 expressed it at barely detectable levels. The 3 cell lines without N-myc amplification also expressed bcl-2 protein at high levels. All NB cell lines tested expressed either c-myc or N-myc protein. These data suggest that in NB, there is no significant association between bcl-2 expression and advanced tumor stages or N-myc amplification. The data also show that bcl-2 expression does not always coincide with myc expression in NB, suggesting that bcl-2- independent mechanisms may exist in the bcl-2-negative NB tumor cells in order to suppress the cell death promoting action of high myc expression.
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PMID:Relationship between bcl-2 and myc gene expression in human neuroblastoma. 776 5

We examined events associated with neuronal differentiation of neuroblastoma cell line SH-SY5Y. Treatment with nerve growth factor (NGF) and aphidicolin, an inhibitor of DNA polymerases alpha and delta, induces terminal differentiation of SH-SY5Y cells. Following 3-4 days of treatment with NGF + aphidicolin, the cells irreversibly ceased proliferation and differentiated. There was a succession of events preceding differentiation. Down-regulation of c-myc was an early event occurring after less than 1 day of treatment with NGF + aphidicolin. Upregulation of the trkA and low-affinity NGF receptors (LNGFR) occurred after 3 days of NGF + aphidicolin treatment and required treatment with both NGF and aphidicolin. To test the role of TrkA in neuroblastic differentiation, we transfected SH-SY5Y cells with a TrkA-expression plasmid. In response to NGF in the absence of aphidicolin, the TrkA-transformant line ceased proliferation and irreversibly differentiated. SH-SY5Y cells bearing a control plasmid displayed only modest, reversible differentiation and did not cease cell proliferation in response to NGF. Hence, expression of NGF receptors is upregulated during differentiation of SH-SY5Y cells, and overexpression of TrkA enhances NGF-induced differentiation.
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PMID:TrkA neurogenic receptor regulates differentiation of neuroblastoma cells. 782 71

The Myc family proteins represented by c-Myc are thought to play a crucial role in cellular proliferation, differentiation, transformation, and apoptosis. In this study, we demonstrated the novel role for a Myc family protein in elicitation of immunogenic phenotypes in tumor cells. Injection of rat 9L or C6 glioma cells, together with the s-myc gene linked to the cytomegalovirus promoter, completely prevented formation of both brain tumors and s.c. tumors derived from the parental glioma cells. However, introduction of the s-myc gene had no inhibitory effect on development of B104-derived neuroblastoma. In addition, unlike the s-myc gene, injection of the c-myc or wild type p53 (wt-p53) gene together with glioma cells did not modulate the tumor immunogenicity and resulted in formation of gliomas in the animals. These findings suggest that s-Myc expression may stimulate the presentation of a tumor antigen common to 9L and C6 cells to T lymphocytes and augment the activity of the host immune system, resulting in prevention of glioma formation in vivo. This success in tumor eradication indicates the possibility of application of the s-myc gene for gene therapy of human brain tumors.
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PMID:Modulation of tumor immunogenicity of rat glioma cells by s-Myc expression: eradication of rat gliomas in vivo. 784 17

There may be a close relationship between myc oncogenes and carcinogenesis of human neuroblastoma. In previous studies, we were able to induce differentiation of certain neuroblastoma cell lines with NGF. In order to study gene regulation during differentiation, N-myc and c-myc cDNA probes were hybridized with RNA extracted from different cell lines before and after NGF treatment. It was found that cell lines which expressed N-myc did not express c-myc while those with c-myc did not express N-myc except for SHEP cell line which had neither c-myc nor N-myc expression. In NGF-induced differentiated neuroblastoma cells, c-myc oncogene was down-regulated in comparison with the control samples. The time course of c-myc down-regulation was concomitant with the appearance of morphological differentiation. In situ hybridization also showed remarkable reduction of c-myc oncogene expression in NGF-induced differentiated cells as compared with the untreated control cells. These results indicate that down-regulation of c-myc oncogene may be a key event during NGF-induced differentiation and over-expression of c-myc oncogene may, at least partially, be responsible for the genesis of neuroblastoma.
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PMID:Down-regulation of c-myc oncogene during NGF-induced differentiation of neuroblastoma cell lines. 786 34

To investigate the possibility of collaboration between telomeric deletion on the short arm of chromosome 1 and genetic amplification similar to that described in human neuroblastoma, 122 human primary breast tumors were examined by restriction fragment length polymorphism analysis for loss of heterozygosity on 1p32-pter and for the three most frequently amplified genetic regions in breast carcinomas (MYC and ERBB2 protooncogenes and the chromosomal region 11q13). Allelic losses at one or more loci on the telomeric part of the short arm of chromosome 1 was observed in 57 (47%) of 122 informative tumors. MYC, ERBB2, and the 11q13 region were amplified in 23, 20, and 21% of breast tumors, respectively. A correlation was found between loss of heterozygosity on chromosome 1p32-pter and amplification of the MYC (formerly c-myc) protooncogene (P = 0.003), suggesting that these two genetic events may collaborate during tumor progression in human breast cancer. These results, together with those obtained in human neuroblastoma, suggest that the distal part of the short arm of chromosome 1 harbors an unidentified tumor suppressor gene(s), whose inactivation may be involved in MYC family gene amplification (an example of genetic instability) in tumors of various cellular origins.
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PMID:A tumor suppressor gene on chromosome 1p32-pter controls the amplification of MYC family genes in breast cancer. 791 73

One of the first oncogenes identified from human tumors was c-myc, which is frequently activated in Burkitt's lymphomas due to chromosomal translocations. Subsequently, members of the myc oncogene family were found to be amplified in neuroblastoma and small-cell lung cancer. In normal cells, Myc activity has been shown to be both necessary and sufficient for resting cells to enter the cell cycle. Interestingly, it appears that Myc not only drives the cell cycle, but also induces cell death by apoptosis in certain situations. Myc contains a transcriptional activation domain and a basic helix-loop-helix-leucine zipper DNA-binding and dimerization domain. As a heterodimer with a structurally related protein, Max, Myc can bind DNA in a sequence-specific manner. These results suggest that the Myc/Max heterodimer functions as a transcriptional activator of genes that are critical for the regulation of cell growth.
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PMID:Myc protein: partners and antagonists. 794 8

In a series of mouse pvt-1 cDNA clones prepared from an immortalized B-cell line that contains an amplified c-myc/pvt-1 region, we have identified a unique cDNA, AJ-I, which contains 57 bp of pvt-1 sequence (pvt-1a) spliced to a novel sequence of 2.1 kb. We report here that this 3' segment (termed AJ-IX) maps more than 60 kb telomeric to pvt-1a and is encoded by a novel locus (AJ-I) on mouse chromosome 15. The AJ-IX probe detects a transcript that is expressed only in normal mouse brain and testis. Several mast-cell tumors, Ly-I+ B-lymphocytic cell lines and a neuroblastoma also display abundant levels of AJ-IX-specific mRNA. However, splicing of pvt-1a to AJ-IX is found exclusively in Ly-I+ B-cell lines that contain amplified c-myc/pvt-1. We conclude that some features in the generation of this amplicon facilitates the synthesis of a pvt-1/AJ-IX chimeric mRNA that may play a role in immortalization of these Ly-I+ B-cell lines.
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PMID:Co-amplification of c-myc/pvt-1 in immortalized mouse B-lymphocytic cell lines results in a novel pvt-1/AJ-1 transcript. 809 75

A method for rapid synchronization of neuroblastoma cells was developed using the thymidine block to arrest cells in the G1-S boundary. Following release from the thymidine block, cells traversed to G2-M in 7-8 h with 85% cell synchrony. Determination of the steady-state level of proliferating cell nuclear antigen (PCNA) mRNA and protein by Northern and Western blots revealed an accumulation of the PCNA messenger RNA transcripts and PCNA protein at G1-S and a rapid decrease when cells entered S phase. The level of both the messenger RNA transcripts and protein increased as the cells moved to late-S and G2-M. Similarly, the steady-state level of c-myc and N-myc messenger RNA transcripts and proteins increased during the G1-S block, decreased when the cells entered S, and increased as the cells moved through S phase to G2-M. However, immunofluorescence staining for PCNA and myc protein indicated a low level of staining for all three proteins at G1-S and a significant increase in staining intensity during S phase. Similarly, immunoelectron microscopy revealed low levels of N-myc and c-myc staining during G1-S and increased staining during mid-S and late S phase of the cell cycle. These results suggest differential cell cycle-dependent accessibility of myc protein and PCNA to staining in the intact cells compared to the whole cell extract. Furthermore, using immunofluorescence staining, confocal microscopy, and immunoelectron microscopy, we demonstrate for the first time that myc proteins are associated with the chromosomes during mitosis.
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PMID:Ultrastructural localization and fluctuation in the level of the proliferating cell nuclear antigen and myc oncoproteins in synchronized neuroblastoma cells. 809 97

Plasmacytomagenesis provides a murine model to decipher progressive genetic events culminating in a B-cell neoplasia. Activation of the c-myc protooncogene by chromosomal translocation is considered an initiating event. Intracisternal A-type particles (IAPs) are defective retroviral-like structures present in the endoplasmic reticulum of plasmacytomas (PCTs). IAP proviral insertions have been documented to engender negative or positive effects on the expression of nearby cellular genes. We have isolated a gene, PANG (plasmacytoma-associated neuronal glycoprotein), that is ectopically transcribed in a number of PCTs due to IAP long terminal repeat (LTR) activation. A full-length PANG cDNA was isolated from an MPC-11 plasma cell tumor cDNA library and encodes a polypeptide of about 113 kDa with six immunoglobulin C2-like and four type III fibronectin-like domains. PANG bears a striking resemblance to axonal glycoproteins TAG-1 and F11 known to function in neuronal outgrowth. An extensive survey revealed a predominant 3.6-kb PANG transcript in 60% (30 of 50) of PCTs as well as unique smaller and larger species. All other normal and transformed lymphoid and nonlymphoid cell lines and normal tissues were negative for PANG expression except for the brain, wherein unique 4.0- and 6.1-kb transcripts were detected. Reverse transcriptase PCR analysis revealed IAP LTR fusion to PANG mRNAs in five PCTs and in a neuroblastoma line. The 5' end of a mouse brain PANG cDNA was identical to the MPC-11 PANG transcript except for the precise replacement of its 5' LTR sequence.
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PMID:PANG, a gene encoding a neuronal glycoprotein, is ectopically activated by intracisternal A-type particle long terminal repeats in murine plasmacytomas. 810 13


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