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)

No systematic approach to detect expression of differentiation-related elements was published so far. The undifferentiated N1E-115 neuroblastoma cell line was switched into a neuronal phenotype by DMSO treatment and used for proteomic experiments. We used two-dimensional gel electrophoresis followed by unambiguous mass spectrometrical identification of proteins to generate a map of cytoskeleton proteins (CPs), i.e., to search for differentiation-related structures. Alpha-actin, actin-like protein 6A, gamma-tubulin complex component 2, tubulin alpha 3/alpha 7, CLIP associating protein 2, B4 integrin interactor homolog were detectable in the undifferentiated cell line exclusively and neuron-specific CPs drebrin and presynaptic density protein 95, actin-related protein 2/3, alpha and beta-centractin, PDZ-domain actin binding protein, actinin alpha 1, profilin II, ezrin, coactosin-like protein, transgelin 2, myosin light polypeptide 6, tubulin alpha 2, 6 and 7, beta tubulin (94% similar with tubulin beta-2), tubulin beta 3, tubulin tyrosine ligase-like protein 1, lamin B1 and keratin 20 were observed in the differentiated cell line only. We herein identified differentiation-related expressional patterns thus providing new evidence for the role of CPs in the process of neuronal differentiation.
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PMID:Cytoskeleton changes following differentiation of N1E-115 neuroblastoma cell line. 1654 50

The function and mechanism of macropinocytosis in cells outside of the immune system remain poorly understood. We used a neuroblastoma cell line, Neuro-2a, to study macropinocytosis in neuronal cells. We found that phorbol 12-myristate 13-acetate (PMA) and insulin-like growth factor 1 (IGF-1) induced two distinct types of macropinocytosis in the Neuro-2a cells. IGF-1-induced macropinocytosis occurs mostly around the cell bodies and requires phosphoinositide 3-kinase (PI3K), while PMA-induced macropinocytosis occurs predominantly in the neurites and is independent of PI3K activity. Both types of macropinocytosis were inhibited by a specific inhibitor of nonmuscle myosin II, blebbistatin. siRNA knockdown of nonmuscle myosin II isoforms, -IIA and -IIB, resulted in opposite effects on macropinocytosis induced by PMA or IGF. Myosin IIA knockdown significantly increased, whereas myosin IIB knockdown significantly decreased, macropinocytosis with correlating changes in membrane ruffle formation.
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PMID:Myosin IIB isoform plays an essential role in the formation of two distinct types of macropinosomes. 1974 71

To identify potential biomarkers of therapy response, we have previously done a large-scale gain-of-function genetic screen to identify genes whose expression confers resistance to histone deacetylase inhibitors (HDACI). This genetic screen identified two genes with a role in retinoic acid signaling, suggesting that HDACIs target retinoic acid signaling as part of their anticancer effect. We study here a third gene identified in this genetic screen, UNC45A, and assess its role in retinoic acid signaling and responses to HDACIs using cell-based proliferation and differentiation assays and transcriptional reporter gene assays. The vertebrate Unc45 genes are known for their roles in muscle development and the assembly and cochaperoning of the muscle motor protein myosin. Here, we report that human UNC45A (GCUNC45) can render transformed cells resistant to treatment with HDACIs. We show that UNC45A also inhibits signaling through the retinoic acid receptor alpha. Expression of UNC45A inhibits retinoic acid-induced proliferation arrest and differentiation of human neuroblastoma cells and inhibits the induction of endogenous retinoic acid receptor target genes. These data establish an unexpected role for UNC45A in causing resistance to both HDACI drugs and retinoic acid. Moreover, our data lend further support to the notion that HDACIs exert their anticancer effect, at least in part, through an effect on retinoic acid signaling.
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PMID:UNC45A confers resistance to histone deacetylase inhibitors and retinoic acid. 1984 31

The efficacy of (131)I-metaiodobenzylguanidine (MIBG) therapy relies on norepinephrine transporter (NET) function. The ionic make-up of the extracellular fluid critically controls neuronal cell activity and can also affect substrate transport. In this study, we explored the effect of treatment with elevated KCl concentration on MIBG uptake in SK-N-SH neuroblastoma cells. KCl stimulation caused a rapid increase of (131)I-MIBG uptake in a manner that was calcium-dependent and accompanied by activation of calcium/calmodulin-dependent protein kinase (CaMK)II. The effect was completely abolished by KN93, an inhibitor of CaMKI, II, and IV. STO609, a selective inhibitor of CaMK kinase required for activation of CaMKI and IV, but not CaMKII, only modestly attenuated the response. The KCl effect was also completely abrogated by ML7, a selective inhibitor of myosin light chain kinase (MLCK). This restricted form of CaMK activates myosin, which is required for vesicle trafficking. Saturation kinetic analysis revealed KCl stimulation to increase maximal transport velocity without affecting substrate affinity. In conclusion, KCl stimulation rapidly upregulates NET function through the CaMK pathway via activation of CaMKII and MLCK. These findings allow a better understanding of how NET function is acutely modulated by the ionic environment, which in turn may ultimately help improve the efficacy of (131)I-MIBG therapy.
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PMID:131I-MIBG targeting of neuroblastoma cells is acutely enhanced by KCl stimulation through the calcium/calmodulin-dependent kinase pathway. 2376 46

Acute osmotic fluctuations in the brain occur during a number of clinical conditions and can result in a variety of adverse neurological symptoms. Osmotic perturbation can cause changes in the volumes of intra- and extracellular fluid and, due to the rigidity of the skull, can alter intracranial pressure thus making it difficult to analyze purely osmotic effects in vivo. The present study aims to determine the effects of changes in osmolarity on SH-SY5Y human neuroblastoma cells in vitro, and the role of the actin-myosin network in regulating this response. Cells were exposed to hyper- or hypoosmotic media and morphological and cytoskeletal responses were recorded. Hyperosmotic shock resulted in a drop in cell body volume and planar area, a persisting shape deformation, and increases in cellular translocation. Hypoosmotic shock did not significantly alter planar area, but caused a transient increase in cell body volume and an increase in cellular translocation via the development of small protrusions rich in actin. Disruption of the actin-myosin network with latrunculin and blebbistatin resulted in changes to volume and shape regulation, and a decrease in cellular translocation. In both osmotic perturbations, no apparent disruptions to cytoskeletal integrity were observed by light microscopy. Overall, because osmotically induced changes persisted even after volume regulation occurred, it is possible that osmotic stress may play a larger role in neurological dysfunction than currently believed.
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PMID:Actin-myosin network influences morphological response of neuronal cells to altered osmolarity. 2580 76


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