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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human neural-crest-derived tumor cell lines, including three neuroblastomas, an astrocytoma, a glioblastoma, a rhabdomyosarcoma and a melanoma were screened for the expression of the integrin alpha 4 beta 1 (VLA-4). The neuroblastomas IMR-32 and SK-N-SH, the astrocytoma 131-INI, the glioblastoma Fogerty and the rhabdomyosarcoma TE-671 expressed alpha 4 beta 1 as determined by cytofluorometry and immunoprecipitation. Another neuroblastoma line, LA-N-1, did not express alpha 4 beta 1. Analysis of immunoprecipitated alpha 4 beta 1 showed that the alpha 4 subunit from the various cell types differed in relative molecular weight (M(r)). The variability in the observed M(r) could be accounted for by differences in the levels of N-linked glycosylation. The observed variability in M(r) did not appear to affect function since intact cells and solubilized alpha 4 beta 1 bound to a synthetic peptide identical in sequence to the CS-1 region of the alternatively spliced IIICS domain of fibronectin, a known alpha 4 beta 1 ligand.
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PMID:Expression and ligand-binding function of the integrin alpha 4 beta 1 (VLA-4) on neural-crest-derived tumor cell lines. 153 75

The RET proto-oncogene, which encodes a receptor tyrosine kinase, displays multiple alternative splicing variants. Splicing of sequences 3' of exon 19 to generate several coding and untranslated region (UTR) sequences has been previously reported. We have sequenced the full length RET coding region and characterized the transcripts and 3' UTRs generated by alternative splicing of the RET 3' terminus. These analyses were performed using both RET cDNA cloned from a pheochromocytoma library and reverse transcriptase PCR products generated using RNA from a neuroblastoma cell line (LA-N-2). Three different carboxyl termini were identified. In addition to the nine and 51 terminal amino acid forms already known, we identified a third with 43 terminal amino acids predicted to encode a novel RET protein isoform. A total of 3621 base pairs of DNA 3' of exon 19, which spans the alternatively spliced exons and RET UTRs, was sequenced. Four polyadenylation sites were identified. The observed combinations of polyadenylation sites and 3' coding sequence suggest that RET transcripts with up to 10 different 3' sequences and up to 40 different full length RET transcripts may exist.
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PMID:Characterization of RET proto-oncogene 3' splicing variants and polyadenylation sites: a novel C-terminus for RET. 747 23

The axonal microtubule-associated protein, tau, is thought to play an important role in axonal growth and in the establishment of neuronal polarity. In adult human brain there are six alternatively spliced tau isoforms, which have different microtubule binding affinities in vitro. The tubulin-tau interaction is further modified by phosphorylation of tau and, compared to adult brain tau, both foetal brain tau and paired helical filament (PHF) tau, characteristic of Alzheimer's disease, are hyperphosphorylated. In vivo both the expression of tau isoforms and their phosphorylation states are developmentally regulated. In order to establish the correlation between the expression of tau isoforms and their pattern of phosphorylation, we have characterised these two features in several in vitro models of neuronal differentiation, including the human neuroblastoma cell lines, SK-N-SH, SH-SY5Y and IMR32 cells, rat PC12 cells and primary rat cortical neurones. Sensitive RT-PCR analysis revealed a different complement of tau isoforms in the different cell lines and neuritogenesis was associated mainly with an increase in the overall tau protein level with no apparent phosphorylation changes. A switch in tau isoform expression occurred only at the terminal stages of neuronal development, when it may be important in reinforcing the previously established axonal cytoarchitecture.
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PMID:Tau isoform expression and phosphorylation state during differentiation of cultured neuronal cells. 749 9

To identify cell adhesion molecules (CAMs) expressed by mammalian motoneurons, we applied the polymerase chain reaction to a murine motor neuron-like cell line, NSC-34. Using primers derived from a group of L1-related CAMs, we cloned two alternatively spliced forms of mouse L1, which differ by a 12-base-pair insert, plus putative murine orthologs of the chicken cell adhesion molecules Nr-CAM/Bravo and neurofascin. All four mRNAs are expressed in NSC-34 cells, but only neurofascin and the insert-minus form of L1 are expressed in its neuroblastoma parent, N18TG2. Analysis of RNA in neonatal tissues reveals expression largely restricted to the brain and spinal cord. In situ hybridization histochemistry of spinal cord shows that motoneurons express L1, Nr-CAM, and neurofascin as well as N-CAM. L1 and N-CAM RNAs are detected throughout the period studied (from embryonic day [E]11 to postnatal day [P]28), whereas Nr-CAM is expressed only at early ages (< E15) and neurofascin is predominantly expressed postnatally. Moreover, each CAM is expressed by distinct subsets of neighboring cells and at distinct times. For example, Nr-CAM mRNA is present in floor plate cells of embryonic spinal cord, whereas neurofascin is expressed by a subset of glia postnatally. Finally, we show that each CAM has a distinct spatiotemporal pattern of expression in dorsal root ganglia.
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PMID:Expression of four immunoglobulin superfamily adhesion molecules (L1, Nr-CAM/Bravo, neurofascin/ABGP, and N-CAM) in the developing mouse spinal cord. 770 55

Two isoforms of brain ankyrin, 440 kDa and 220 kDa ankyrinB, which are products of alternatively spliced pre-mRNA encoded by a single gene, are both expressed in human neuroblastoma NB-1 cells. Expression of the polypeptide and mRNA of the larger isoform increased upon induction of neurite outgrowth in NB-1 cells by dibutyryl cAMP, while those of the smaller isoform were unaffected. The expressed 440 kDa ankyrinB was concentrated at the tip of growing neurites and was partly co-localized with GAP-43. These results suggest that 440 kDa ankyrinB is one of the neuronal growth-associated proteins and provides an interesting example of gene regulation by alternative splicing in neuronal cells.
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PMID:Possible involvement of the 440 kDa isoform of ankyrinB in neuritogenesis in human neuroblastoma NB-1 cells. 780 94

Neuroblastoma, the most common malignant solid cancer of children, has an ability to differentiate in vitro and in vivo. This biological property has a significant influence upon the prognosis of patients with neuroblastomas. Neuronal cells express three alternatively spliced forms of c-src mRNA (nonneuronal c-src, neuronal c-srcN1, and neuronal c-srcN2), which are found at different levels in adult and fetal human brain tissue. In this study, the transcriptional levels of the three c-src mRNAs were examined in relation to the neural differentiation in eight human neuroblastoma cell lines and two clonal sublines and in seven primary neuroblastoma tissues by S1 nuclease protection assays. Neuronal c-srcN1 mRNA was expressed at high levels in neuroblastoma cell lines with the ability to differentiate but not in the cell lines lacking the capacity to mature in response to chemical inducers irrespective of N-myc gene amplification and overexpression. In terminally differentiated neuroblastoma cells, the expression of neuronal c-srcN2 mRNA, which was barely detectable at a steady-state level in the uninduced cells, increased to significant levels. Infantile neuroblastomas identified by mass screening tests expressed both neuronal c-srcN1 and c-srcN2 mRNAs at levels almost identical to that found in human brain tissue, but terminally differentiated neuroblastoma cells, neuroblastomas from older children identified based on clinical symptoms, did not. These results suggest that neuronal c-src expression and the ability of neuroblastomas to differentiate in vitro and in vivo may be correlated.
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PMID:Expression of alternatively spliced src messenger RNAs related to neuronal differentiation in human neuroblastomas. 831 27

Two alternatively spliced mouse lymphocyte and brain ltk cDNAs predict small transmembrane tyrosine kinases that use CUG translational start codons and that differ upstream of their transmembrane segment. A recently isolated human neuroblastoma ltk cDNA, in contrast, includes a regular AUG start codon and predicts a more conventional receptor kinase with a larger N-terminal segment. This raised the suggestion that previous mouse cDNAs may have been aberrantly spliced or incomplete and questioned the significance of a recent study that localized the lymphoid ltk protein to the endoplasmic reticulum. Here we show that mice tissue-specifically express four ltk mRNAs. In addition to the two previously described lymphoid and brain mRNAs, we now describe two mRNAs from C1300 neuroblastoma cells that start with five exons which are absent from lymphoid or brain transcripts. The pair of C1300 mRNAs differ by the same alternatively spliced exon that distinguishes brain from lymphoid mRNAs and predict much larger receptor-type kinases that use regular AUG start codons. Our results also show that at least one of the larger, more conventional C1300 ltk receptors shares the endoplasmic reticulum localization of the shorter lymphoid protein.
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PMID:Four tissue-specific mouse ltk mRNAs predict tyrosine kinases that differ upstream of their transmembrane segment. 838 Sep 20

The multimodular glycoprotein tenascin-C is transiently expressed, predominantly by glial cells, during the development of the central and peripheral nervous systems. This extracellular matrix glycoprotein is involved in the control of cell adhesion, neuron migration and neurite outgrowth. Distinct functional properties for neuronal cell types have been attributed to separate tenascin-C domains using antibody perturbation studies and in vitro experiments on tenascin-C fragments. In order to study potential roles of tenascin-C for glial cell biology, a library of recombinant tenascin-C domains was used in a bioassay in vitro. Embryonic day 14 astrocytes, various astroglial-derived cell lines (C6, A7 and Neu7) and oligodendroglial-derived cell types (Oli-neu and G26-20) were examined in an adhesion assay and compared to the neuroblastoma cell line N2A. A binding site for most cell types, except for A7 and N2A, could be assigned to the first three fibronectin type III domains. Repulsive properties could be mapped to three different sites the epidermal growth factor-like repeats, fibronectin type III repeats 4 and 5 and to the alternatively spliced region of the molecule. The responses to these repulsive sites varied according to the cell type. These data are consistent with the interpretation that different cell types express distinct sets of tenascin-C receptors which might regulate cellular responses via distinct second messenger pathways.
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PMID:Glial cell interactions with tenascin-C: adhesion and repulsion to different tenascin-C domains is cell type related. 884 7

DCC (deleted in colorectal cancer), a candidate tumor suppressor gene located in chromosome band 18q21.2, encodes a transmembrane protein of 1447 amino acids. Neogenin, a protein with nearly 50% amino acid identity to DCC, was recently identified because of its dynamic expression in the developing nervous system and gastrointestinal tract of the chicken. To explore a role for the human neogenin (NGN) gene in cancer, we have isolated cDNAs for two alternatively spliced forms of NGN, encoding proteins of 1461 and 1408 amino acids. Fluorescence in situ hybridization studies (FISH) localized NGN in chromosome band 15q22, a region infrequently affected by alterations in cancer. NGN transcripts of about 7.5 and 5.5 kb were detected in all adult tissues studied. In contrast to the frequent loss of DCC expression, no alterations in NGN expression were observed in more than 50 cancers studied, including glioblastoma, medulloblastoma, neuroblastoma, colorectal, breast, cervical and pancreatic cancer cell lines and xenografts. Based on their sequence conservation and similar expression during development, DCC and NGN may have related functions. However, the chromosomal location and ubiquitous expression of NGN in various human tumors suggest it is infrequently altered in cancer.
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PMID:Identification and characterization of neogenin, a DCC-related gene. 912 61

Using the technique of differential display-polymerase chain reaction (DD-PCR), we isolated a cDNA fragment that is over-expressed in glioblastoma multiforme tissue as compared to normal brain tissue. Sequence analysis indicated that this sequence is identical to the previously isolated human neuron-glia-related cell adhesion molecule hNr-CAM. Gene-specific RT-PCR analysis indicated that hNr-CAM is over-expressed in high-grade astrocytomas, gliomas and glioblastoma tumor tissues as compared to normal brain tissue. High levels of hNr-CAM expression also were observed in cell lines derived from astrocytomas, gliomas and glioblastoma multiforme tumors. Low levels of hNr-CAM expression were observed in neuroblastoma, meningiomas, melanoma, normal breast and prostate tumor tissues. Northern blot analysis showed an alternatively spliced mRNA of 1.4 kb in several tumors as compared to the 7.5 kb transcript found in normal brain tissue. Genomic Southern blot analysis of DNA from 3 brain tumor cell lines showed that over-expression of hNr-CAM in brain tumors was not due to gene amplification. In situ hybridization analysis indicated that 11 of the 20 human brain tumor samples studied showed hNr-CAM over-expression. Our results suggest that hNr-CAM is over-expressed in malignant brain tumors and can serve as a novel marker for brain tumor detection and perhaps therapy.
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PMID:Cell adhesion molecule Nr-CAM is over-expressed in human brain tumors. 959 Jan 16


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