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)

The human ret proto-oncogene (proto-ret), encoding a receptor tyrosine kinase, is highly expressed in neuroblastomas, medullary thyroid carcinomas (MTCs) and pheochromocytomas, which are all tumors of cells originating from the neural crest. In studies on the transcription mechanism of proto-ret, we identified the transcription start site and the promoter region by chloramphenicol acetyl transferase (CAT) assay. A sequence upstream from the transcription start site (-167 to +98 bp) showed definite promoter activity in both proto-ret mRNA-positive neuroblastoma NB39-nu cells and proto-ret mRNA-negative HeLa cells. The promoter sequence had a high GC content and contained four tandemly repeated GC boxes without a TATA box. Putative binding sequences for SP-1, AP-2 and epidermal growth factor receptor-specific transcription factor (ETF) and also the transcription-suppressing factor, GC factor (GCF), were found in the repeated GC box region. Southern blot analysis of DNAs of neuroblastoma cell lines and primary MTCs showed that the high proto-ret expression in these tumors is not caused by gross genetic changes in the promoter region, suggesting the possible involvement of a region(s) other than the sequence from -167 to +98 bp or a minor genetic change(s) in the promoter region.
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PMID:Identification and analysis of the ret proto-oncogene promoter region in neuroblastoma cell lines and medullary thyroid carcinomas from MEN2A patients. 135 Jun 70

The product of the retTPC oncogene, an activated form of the ret proto-oncogene found in human papillary thyroid carcinomas, was identified as a 57-kDa protein (p57retTPC) by Western blotting with a polyclonal antibody raised by an oligopeptide corresponding to the carboxy-terminal region of the ret proto-oncogene product. Subcellular fractionation experiments using NIH3T3 cell transformants induced by the retTPC cDNA showed that p57retTPC was localized in a soluble cytoplasmic fraction, whereas the ret proto-oncogene products expressed in a neuroblastoma cell line were present in a membrane fraction. Immunostaining also demonstrated that p57retTPC is localized in the cytoplasm. Immunoprecipitation with anti-phosphotyrosine antibody followed by Western blotting revealed that p57retTPC is constitutively phosphorylated, whereas the ret proto-oncogene products are not. These findings suggest that p57retTPC has an aberrant tyrosine kinase activity resulting in autophosphorylation associated with change in its location.
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PMID:Detection of phosphorylated retTPC oncogene product in cytoplasm. 162 May 55

We examined the expression of ret proto-oncogene (proto-ret) in surgically resected human neuroblastomas. Slot blot RNA hybridization revealed that all 29 neuroblastomas examined expressed the proto-ret, the relative intensity of the hybridization ranging from 1 to 48. No correlation was found between the level of expression of proto-ret and the clinical stage. The level of expression was also not correlated with N-myc amplification, the patient's age or the histological type of the tumor. Based on the previous finding that proto-ret expression is very rarely detected in tumor cell lines other than those of neuroblastoma, proto-ret expression was suggested to be a characteristic of neuroblastomas, and possibly to be involved in the genesis of neuroblastomas.
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PMID:Expression of ret proto-oncogene in human neuroblastomas. 169 38

Previously we observed specific expression of the ret proto-oncogene (proto-ret) in human neuroblastoma cell lines. A neuronal subline and non-neuronal sublines were isolated from the SK-N-SH cell line, which is composed of a heterogeneous cell population. Expression of proto-ret was detected in the neuronal subline, named SH-4305, but not in three non-neuronal sublines. Expression of proto-ret in the SH-4305 cells increased markedly after treatment with retinoic acid for 1 day, with concomitant morphological change, namely neurite outgrowth, and induction of neurofilament mRNA expression. Induction of proto-ret expression seemed to be correlated with neurite outgrowth and increase of neurofilament mRNA expression. These data suggest that the proto-ret product plays a role in neuronal differentiation.
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PMID:Expression of the ret proto-oncogene in human neuroblastoma cell lines and its increase during neuronal differentiation induced by retinoic acid. 176 78

Monoclonal and/or polyclonal antibodies were generated against the products synthesized from two portions of the ret proto-oncogene (c-ret) cDNA expressed in Escherichia coli. These antibodies were reactive in immunoblotting with 150 kd and 170 kd proteins in cell lysates from three human neuroblastoma cell lines expressing the ret proto-oncogene. When the neuroblastoma cells were treated with tunicamycin, a protein with an apparent molecular weight of 120 kd, which is consistent with that of the c-ret protein predicted from the cDNA sequence, appeared on immunoblots. These results indicated that the 150 kd and 170 kd proteins in neuroblastoma cells are produced from a single polypeptide of 120 kd by posttranslational glycosylation. Furthermore, the antibodies detected a unique 190 kd protein as well as 150 kd protein in a cell lysate from THP-1 human monocytic leukemia cell line, suggesting that glycosylated forms of the c-ret protein are different between neuroblastoma and leukemia cells.
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PMID:Identification of the ret proto-oncogene products in neuroblastoma and leukemia cells. 200 Feb 22

The ret proto-oncogene expresses four major mRNA species of different lengths in human malignant cell lines and rat tissues. We isolated ret proto-oncogene cDNA clones from a cDNA library of a human neuroblastoma line, Nagai, which over-expressed these mRNAs. Four cDNA clones differing from each other in their 3' portions were analysed. The sequence of the region common to the cDNA clones is essentially identical to a reported cDNA sequence derived from THP-1 monocytic leukemia cells, that encodes a protein with characteristic features of receptor-type tyrosine kinase. From the 3' heterogeneity, two isoforms of the ret proto-oncogene product of 1072 and 1114 residues that differed from each other in their 9 and 51 C-terminal amino acids are predicted. Comparison of the structures of cDNA clones with that of the genomic clone showed that the 3' heterogeneity is produced by alternative polyadenylation and splicing of mRNA. Northern blot analysis using various fragments of cDNA indicated that the 4.5 kb, 3.9 kb and possibly 7.0 kb transcripts may encode a protein of 1072 residues, while the 6.0 kb transcript and a (minor) 4.6 kb transcript may encode a protein of 1114 residues.
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PMID:Characterization of ret proto-oncogene mRNAs encoding two isoforms of the protein product in a human neuroblastoma cell line. 218 80

The expression of the ret proto-oncogene (proto-ret), which possibly encodes two isoforms of a receptor-type tyrosine kinase, was examined in human tumor cell lines. Expression of the proto-ret mRNA was detected in all 11 neuroblastoma cell lines examined. The level of mRNA varied more than 100-fold in these neuroblastoma cell lines and was particularly high in three of them. On the other hand, 19 non-neuroblastoma tumor cell lines derived from solid tumors and a human diploid fibroblast cell line did not express any detectable levels of proto-ret mRNA. No remarkable amplification of the proto-ret or gross structural changes in the coding region were found in these neuroblastoma cell lines. The specific expression of the proto-ret in neuroblastomas suggests that the proto-ret product may have a role in cellular functions specific to neuroblastoma cells.
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PMID:Specific expression of the ret proto-oncogene in human neuroblastoma cell lines. 221 55

In a papillary thyroid carcinoma cell line, TPC-1, we found transcripts hybridizing to ret proto-oncogene (proto-ret) cDNA probes. The transcripts hybridized to the probes encoding the kinase domain but not to those of the transmembrane and extracellular domains of proto-ret. The sizes of the main transcripts in TPC-1 were aberrant, being 2.0, 2.5, 4.0 and 5.0 kb. In the neuroblastoma cell lines, the transcripts were 3.9, 4.5, 6.0 and 7.0 kb, which have been proved to be generated by alternative splicing and polyadenylation from the non-altered proto-ret oncogene. All of the four transcripts in TPC-1 are about 2 kb smaller than the corresponding ones in the neuroblastoma. From the length of the transcripts, it is suspected that the transcripts in TPC-1 are a rearranged form of proto-ret. This is the first report describing the aberrant transcripts of proto-ret in a human tumor.
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PMID:Presence of aberrant transcripts of ret proto-oncogene in a human papillary thyroid carcinoma cell line. 251 41

We investigated tyrosine kinase activity of the ret proto-oncogene products (proto-Ret proteins), using a cell lysate of NB-39-nu neuroblastoma cells. The 150 kDa and 170 kDa proto-Ret proteins immunoprecipitated with antibodies against their carboxy-terminal 20 amino acids were shown to be phosphorylated predominantly on tyrosine residues in immunocomplex kinase assay. The level of tyrosine phosphorylation of the 150 kDa proto-Ret protein was approximately 10-fold higher than that of the 170 kDa proto-Ret protein, although both proteins were expressed at similar levels in neuroblastoma cells. This result was confirmed by using a lysate of SK-N-MC human primitive neuroectodermal tumor cells transfected with the ret proto-oncogene. The kinase activity of proto-Ret proteins was significantly inhibited by antibodies against their kinase domain, indicating that these antibodies recognize crucial epitopes for the enzymatic activity. On the other hand, the proto-Ret proteins were not phosphorylated in vivo in NB-39-nu cells and SK-N-MC transfectants.
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PMID:Tyrosine kinase activity of the ret proto-oncogene products in vitro. 768 95

The histological localization of the ret proto-oncogene (proto-ret) product was examined in neural crest-derived and neuronal tissues together with their neoplastic counterparts by immunohistochemistry using a polyclonal antibody. Schwann cells, neurons, sympathetic ganglia, and cells of the adrenal medulla were positive for the proto-ret product, whereas melanocytes were negative. Positive results were obtained from neural crest-derived tumours such as schwannoma (69 per cent, 11/16), neurofibroma (59 per cent, 13/22), neuroblastoma (80 per cent, 4/5), phaeochromocytoma (100 per cent, 3/3) and medullary thyroid carcinoma (100 per cent, 3/3). The antibody reacted with all of the 22 astrocytomas examined. With negative proto-ret expression in melanocytic tumours, proto-ret expression was considered to correlate with the differentiation of some lineages of neural crest-derived cells.
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PMID:Expression of the ret proto-oncogene product in human normal and neoplastic tissues of neural crest origin. 819 28


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