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 expression of two cadherins, N- and R-cadherin, was mapped in the CNS of chicken embryos of 6-11 d incubation, focusing on the sensory and motor fiber systems. In the spinal cord, the laterally located fibers of the dorsal funiculus express N-cadherin while the medially located fibers do not. These two fiber systems have a different course within the CNS but associate to form the spinal dorsal roots. In the hindbrain, N-cadherin is expressed by the descending trigeminal (general somatic sensory) tract, which is contiguous with the N-cadherin-positive zone of the dorsal funiculus of the spinal cord. R-cadherin is not expressed by sensory fibers, but is expressed by the visceral motor system of the vagus and glossopharyngeal nerves, which are N-cadherin negative. The motor neurites expressing R-cadherin have a different course within the brain than the sensory neurites expressing N-cadherin, although they form the common sensory/motor roots of the vagus nerve at the surface of the brain. The possibility that N-cadherin provides a guidance cue for sensory axon migration within the CNS by a homophilic adhesion mechanism was investigated in vitro. Explants from sensory spinal ganglia expressing N-cadherin were placed on N-cadherin-transfected neuroblastoma cells, and axon outgrowth was visualized. Results showed that the sensory axons defasciculate and closely follow the cell-cell boundaries between transfected cells where high levels of N-cadherin are expressed. These results show that the two cadherins, like members of the immunoglobulin superfamily of molecules, are expressed in a topographically restricted fashion during chick brain development. They furthermore suggest that N-cadherin expression by neurites may play a role in guiding these neurites along CNS paths that express the same molecule.
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PMID:Restricted expression of N- and R-cadherin on neurites of the developing chicken CNS. 152 94

Cadherins are a family of molecules mediating Ca(2+)-dependent cell-cell adhesion in various tissues. N- and R-cadherin are expressed in the chick embryonic CNS and differ in their expression pattern during development. Here we focus on the differential expression of N- and R-cadherin in the early optic nerve. N-cadherin is expressed by the retinal neurites growing through the optic nerve. R-cadherin is expressed by the early optic nerve glia, which derives from the optic stalk neuroepithelium and corresponds to an immature form of the type-1 astrocyte described in rat optic nerve. The close contact between the plasma membranes of the retinal neurites and the optic nerve glia is believed to be important in guiding retinal axons through the optic nerve. Using neuroblastoma cell lines transfected with R-cadherin, we demonstrate that the N-cadherin-positive retinal axons can use R-cadherin as a substrate for axon elongation. These results suggest that the R-cadherin expressed by the early optic nerve glia might provide a molecular substrate for the growth of N-cadherin-positive retinal axons through the optic nerve.
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PMID:N- and R-cadherin expression in the optic nerve of the chicken embryo. 822 58

Osteogenic protein-1 (OP-1) is a member of the TGF-beta superfamily that is expressed in the nervous system. We recently showed that human recombinant osteogenic protein-1 (hOP-1) strongly promotes the aggregation of dividing neuroblastoma x glioma hybrid NG108-15 cells, in part by inducing the major isoforms of the neural cell adhesion molecule (N-CAM) (Perides, G., Safran, R. M., Rueger, D. C., and Charness, M. E. (1992) Proc. Natl. Acad. Sci. U. S. A. 89, 10326-10330). Here we show that hOP-1 induces L1 expression approximately 6-fold in NG108-15 cells without changing the levels of N-cadherin, neurofilament 200, Thy-1, tau, and G alpha s. OP-1 induction of L1 and N-CAM was unassociated with changes in cell proliferation and was not reproduced by cellular differentiation. The increased adhesiveness of hOP-1-treated NG108-15 cells could be inhibited in part by Fab fragments of an anti-L1 polyclonal antiserum. L1 and N-CAM expression first increased 12-18 h after hOP-1 treatment, reached a maximum after 2-3 days, persisted for up to 5 days, and returned to control levels 3 days after hOP-1 withdrawal. The increases in L1 and N-CAM protein levels were preceded or accompanied by large increases in the abundance of L1 and all detectable N-CAM mRNAs. Actinomycin D prevented the induction by hOP-1 of L1 and N-CAM mRNAs, suggesting that hOP-1 regulates immunoglobulin CAM gene transcription. OP-1 is the first described growth factor that regulates both N-CAM and L1 gene expression.
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PMID:Osteogenic protein-1 regulates L1 and neural cell adhesion molecule gene expression in neural cells. 822 84

The subcommissural organ (SCO) is a specialized ependymal structure of the brain that secretes glycoproteins into the cerebrospinal fluid (CSF), which condense to form a thread-like structure - Reissner's fiber (RF). The effects of soluble material released by RF were examined on neuroblastoma B104 cells grown in serum-free medium, using "low-density" and "high-density" culture systems. In the presence of soluble RF material, low-density cultures were suitable for analysis of the enhanced neurite outgrowth of B104 cells, while high-density cultures allowed the increased B104 cell aggregation to be examined. RF-induced neuronal aggregation and neuritic outgrowth were restricted to a perimeter around the RF. This standardized cell culture system reproduced in part the effects observed previously with primary cortical and spinal cord cell cultures and may serve the analysis of the mechanisms leading to aggregation and neurite outgrowth. In the present study, we analyzed variations in the rate of neural cell adhesion molecules, such as N-CAM and N-cadherin, induced by soluble RF material in high-density cultures.
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PMID:Neuroblastoma B104 cell line as a model for analysis of neurite outgrowth and neuronal aggregation induced by Reissner's fiber material. 1057 Nov 12

Cadherins are Ca(2+)-dependent cell-cell adhesion molecules which play crucial roles in the cell-cell interactions during development, tumorigenesis and metastasis. The absence of N (neural)-cadherin is correlated with the onset of neural crest migration and its reappearance is correlated with the cessation of migration and precedes gangliogenesis. We investigated the expression of cadherins including N-cadherin in five cell lines and eleven clinical specimens of human neuroblastomas, which originated from neural crest cells. We found that three of the neuroblastoma cell lines and all the clinical specimens were positive for the expression of the N-cadherin protein. The other two neuroblastoma cell lines were negative for the expression suggesting they originated from migrating neural crest cells. All these cell lines and clinical samples expressed either cadherin-6, cadherin-11 or both, i.e. cadherins expressed on neural crest cells, supporting their neural crest origin.
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PMID:The expression of cadherins in human neuroblastoma cell lines and clinical tumors. 1081 Mar 77

The deleted in colorectal cancer (DCC) protein is important in the pathway guidance of cells and cell processes during neural development, and DCC has also been implicated in the aberrant cellular migrations of neuroblastoma dissemination. We attempted to further define DCC protein function by the overexpression of full-length and truncated DCC constructs in a human neuroblastoma cell line. Overexpression of the truncated DCC protein resulted in a less epithelioid morphology. This was accompanied by decreases in expression of N-cadherin and alpha- and beta-catenin by immunoblot and Northern blot analysis. Levels of desmoglein were relatively less affected, whereas endogenous DCC protein levels were increased in the truncated transfectants. N-cadherin immunofluorescence was consistent with the immunoblot studies and localized the protein to the cytoplasm and sites of cell-cell contact. Cell aggregation studies demonstrated diminished calcium-dependent aggregation in the truncated transfectants. In conclusion, overexpression of a truncated DCC protein in neuroblastoma cells resulted in the loss of an epithelioid morphology, diminished expression of N-cadherin and alpha- and beta-catenin, and diminished calcium-dependent cell adhesion. These studies provide the first evidence of an apparent functional link between DCC and N-cadherin/catenin-dependent cell adhesion.
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PMID:Truncated DCC reduces N-cadherin/catenin expression and calcium-dependent cell adhesion in neuroblastoma cells. 1123 42

Plakoglobin and its homologue beta-catenin are cytoplasmic proteins that mediate adhesive functions by interacting with cadherin receptors and signaling activities by interacting with transcription factors. It has been suggested that plakoglobin can suppress tumorigenicity whereas beta-catenin can act as an oncogene. We investigated the correlation between the expression pattern of N-cadherin, beta-catenin, and plakoglobin and tumor behavior in primary tumors of 20 neuroblastoma patients of all stages and in 11 human neuroblastoma cell lines. N-cadherin and beta-catenin were detected in 9 of 11 and 11 of 11 cell lines, respectively, whereas plakoglobin was undetectable or severely reduced in 6 of 11 cell lines. Tumor cells from 16 of 20 patients expressed N-cadherin and 20 of 20 patients expressed beta-catenin at levels similar to those of normal ganglion cells. Plakoglobin was undetectable in 9 of 20 tumors. Plakoglobin deficiency in the primary tumors was significantly associated with adverse clinical outcome. Five of the patients with plakoglobin-negative tumors died whereas four patients are alive without evident disease. In contrast, all patients with plakoglobin-positive tumors are alive; 2 of 11 are alive with the disease and 9 of 11 are alive without evident disease. These results suggest that down-regulation of plakoglobin may be of prognostic value for neuroblastoma patients as predictor of poor outcome.
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PMID:Reduced expression of plakoglobin correlates with adverse outcome in patients with neuroblastoma. 1143 52

We studied effects of the familial Alzheimer's disease presenilin 1 (PS1) exon 9 deletion (PS1-DeltaE9) mutation on basal and carbachol-stimulated phosphoinositide (PI) hydrolysis and intracellular Ca(2+) concentrations ([Ca(2+)](i)) in human SH-SY5Y neuroblastoma cells. We demonstrate that PS1-DeltaE9 cells have an enhanced basal PI hydrolysis and [Ca(2+)](i) as compared with both wild type PS1 (PS1-WT) and nontransfected (NT) cells. Both were reversed by the phospholipase C (PLC) inhibitor neomycin. The PS1-DeltaE9-related high basal [Ca(2+)](i) was also reversed by xestospongin C confirming that this effect was inositol trisphosphate receptor-mediated. Carbachol gave a greater stimulation of [Ca(2+)](i) in PS1-DeltaE9 cells that took longer to return to basal as compared with responses seen in NT and PS1-WT cells. This long tail-off effect seen in PS1-DeltaE9 cells after carbachol stimulation was reversed by xestospongin C and dantrolene, suggesting that it was mediated by inositol trisphosphate receptor and ryanodine receptor amplification of Ca(2+). Ruthenium red only reduced carbachol peak elevations of [Ca(2+)](i) in NT and PS1-WT cells and not in PS1-DeltaE9 cells. No significant between cell type differences were seen for basal and carbachol-stimulated [Ca(2+)](i) with either ryanodine or the endoplasmic reticulum Ca(2+) ATPase inhibitor cyclopiazonic acid. Immunostaining experiments revealed that for all the cell types PS1 is present at the plasma membrane and co-localizes with N-cadherin, a component of the cell-cell adhesion complex. Immunoblotting of cell extracts for PLC-beta1 showed that, compared with NT and PS1-WT cells, the PS1-DeltaE9 transfectants gave a relative increase in levels of the calpain generated N-terminal fragment (100 kDa) over full-length (150 kDa) PLC-beta1. Our results suggest that the PS1-DeltaE9 mutation causes upstream changes in PI signaling with enhanced basal PLC activity as a primary effect that leads to a higher [Ca(2+)](i). This may provide a novel mechanism by which the PS1-DeltaE9 mutation sensitizes cells to apoptotic stimuli and enhanced amyloid beta generation.
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PMID:The presenilin 1 deltaE9 mutation gives enhanced basal phospholipase C activity and a resultant increase in intracellular calcium concentrations. 1212 68

The amyloid precursor protein (APP) metabolism is central to pathogenesis of Alzheimer's disease (AD). Parenchymal amyloid deposits, a neuropathological hallmark of AD, are composed of amyloid-beta peptides (Abeta). Abeta derives from the amyloid precursor protein (APP) by sequential cleavages by beta- and gamma-secretases. Gamma-secretase cleavage releases the APP intracellular domain (AICD), suggested to mediate a nuclear signaling. Physiologically, AICD is seldom detected and thus supposed to be rapidly degraded. The mechanisms responsible of its degradation remain unknown. We used a pharmacological approach and showed that several alkalizing drugs induce the accumulation of AICD in neuroblastoma SY5Y cell lines stably expressing APP constructs. Moreover, alkalizing drugs induce AICD accumulation in naive SY5Y, HEK and COS cells. This accumulation is not mediated by the proteasome or metallopeptidases and is not the result of an increased gamma-secretase activity since the gamma-secretase cleavage of Notch1 and N-Cadherin is not affected by alkalizing drug treatments. Altogether, our data demonstrate for the first time that alkalizing drugs induce the accumulation of AICD, a mechanism likely mediated by the endosome/lysosome pathway.
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PMID:Intracellular pH regulates amyloid precursor protein intracellular domain accumulation. 1720 30

Emerging evidence has shown that GSK3beta plays a pivotal role in regulating the specification of axons and dendrites. Our previous study has shown a novel GSK3beta interaction protein (GSKIP) able to negatively regulate GSK3beta in Wnt signaling pathway. To further characterize how GSKIP functions in neurons, human neuroblastoma SH-SY5Y cells treated with retinoic acid (RA) to differentiate to neuron-like cells was used as a model. Overexpression of GSKIP prevents neurite outgrowth in SH-SY5Y cells. GSKIP may affect GSK3beta activity on neurite outgrowth by inhibiting the specific phosphorylation of tau (ser396). GSKIP also increases beta-catenin in the nucleus and raises the level of cyclin D1 to promote cell-cycle progression in SH-SY5Y cells. Additionally, overexpression of GSKIP downregulates N-cadherin expression, resulting in decreased recruitment of beta-catenin. Moreover, depletion of beta-catenin by small interfering RNA, neurite outgrowth is blocked in SH-SY5Y cells. Altogether, we propose a model to show that GSKIP regulates the functional interplay of the GSK3beta/beta-catenin, beta-catenin/cyclin D1, and beta-catenin/N-cadherin pool during RA signaling in SH-SY5Y cells.
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PMID:GSKIP, an inhibitor of GSK3beta, mediates the N-cadherin/beta-catenin pool in the differentiation of SH-SY5Y cells. 1983 Jul 2


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