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

SH-SY5Y neuroblastoma cells undergo neuronal differentiation and their proliferation is inhibited when they are treated with phorbol 12-myristate 13-acetate (PMA). Insulin and insulin-like growth factor I (IGF-I) are mitogens for the nontreated SH-SY5Y cells, whereas the proliferative response to such factor stimulation is lost upon differentiation, in spite of the fact that the receptors for insulin and IGF-I remain expressed and functional in the differentiated cells. Here we show that the PMA-induced differentiation of SH-SY5Y cells grown in a serum-free medium is strongly potentiated by nanomolar concentrations of IGF-I, as judged by morphology and markers for neuronal differentiation--e.g., neuropeptide tyrosine and growth-associated protein 43. Also, insulin and IGF-II potentiated the phorbol ester-induced differentiation, although less efficiently than IGF-I. Using blocking anti-receptor antibodies, it could be shown that the differentiation induced by these factors, in combination with PMA, was primarily mediated through the IGF-I receptor.
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PMID:Insulin-like growth factor I shifts from promoting cell division to potentiating maturation during neuronal differentiation. 194 68

The SH-SY5Y human neuroblastoma cell line is differentiated in vitro with nanomolar concentrations of 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Untreated cells express insulin receptors, and both type I and type II insulin-like growth factor (IGF) receptors, as has been shown by agonist binding and immunoprecipitation studies. Via interaction with its own receptor and the IGF-I receptor, insulin induced a mitogenic response in these cells. IGF-I and IGF-II are also mitogens for SH-SY5Y cells, as shown by a transient increase of the c-fos mRNA level, ornithin decarboxylase activity, thymidine incorporation, and, finally, cell division. TPA-differentiated cells do not respond mitogenically to any of these factors, although insulin and IGF-I receptors are still present on the cell surface and remain functional, as demonstrated by ligand-stimulated autophosphorylation, actin reorganization, and c-fos induction. However, other prereplicative responses, i.e., increased ornithin decarboxylase activity and c-myc mRNA levels, cannot be induced. These phenomena, may be part of a receptor uncoupling mechanism(s). The findings are discussed in terms of differentiation stage-dependent signaling of growth factor receptors. We suggest that these receptors switch from controlling cell division in replicative neuronal cells to mediating externally controlled functions related to the differentiated neuronal phenotype.
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PMID:Mitogenically uncoupled insulin and IGF-I receptors of differentiated human neuroblastoma cells are functional and mediate ligand-induced signals. 215 61

Insulin and IGF-I binding to neuroblastoma cells (SK-N-MC) was increased by 13% and 7% respectively following a 24hr, incubation with the sulphonylurea glyburide. This increase in binding was associated with increased steady-state levels of insulin receptor and IGF-I receptor mRNA levels. Though insulin and IGF-I both stimulate glucose uptake into these cells, the increased binding following glyburide treatment was not associated with any change in glucose uptake.
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PMID:Insulin and IGF-I receptors in neuroblastoma cells: increases in mRNA and binding produced by glyburide. 255 56

The neuroblastoma cell line SH-SY5Y was cultured in the presence of TPA for three days. Increased neurite formation was noted as early as 24 hours after TPA was added. These changes were associated with an increase in IGF-I receptor binding as well as increased mRNA for the IGF-I receptor.
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PMID:TPA-induced neurite formation in a neuroblastoma cell line (SH-SY5Y) is associated with increased IGF-I receptor mRNA and binding. 277 Apr 53

Mouse neuroblastoma N18 cells contain specific high affinity insulin and insulin-like growth factor-I (IGF-I) receptors. Insulin and IGF-I induce phosphorylation, in intact cells, of their respective receptor beta subunits. The insulin receptor beta subunit is represented by a 95-kDa phosphoprotein that is recognized by a specific antiserum (B10). The IGF-I receptor beta subunit is represented by two phosphoproteins of molecular mass 95 and 105 kDa. The hormone-induced phosphorylation was rapid and dose-dependent occurring on both phosphoserine and phosphotyrosine residues. In addition, both insulin and IGF-I induced phosphorylation of an endogenous protein of molecular mass 185 kDa (pp185). The rapidity and dose dependency of the phosphorylation of pp185 suggested that it may represent a common endogenous substrate for the insulin and IGF-I receptors in these neural-derived cells. Phosphorylation was primarily on phosphoserine and phosphotyrosine residues. pp185 did not absorb to wheat germ agglutinin-agarose and was not stimulated by either epidermal growth factor or platelet-derived growth factor. The finding of pp185 in these neural-related cells as well as in non-neural tissues suggests that it may represent a ubiquitous endogenous substrate for both the insulin and IGF-I receptor kinases.
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PMID:Insulin and insulin-like growth factor-I stimulate a common endogenous phosphoprotein substrate (pp185) in intact neuroblastoma cells. 296 Jun 69

We have characterized receptors for the insulin-like growth factor (IGF-I) on the mouse neuroblastoma cell line N18 as well as NG108, the hybrid cell line of N18 and rat glioma (C6). In this cell-free system, IGF-I and insulin stimulated the phosphorylation of 95-kDa and 105-kDa proteins. Using appropriate antibodies we were able to demonstrate that the IGF-I receptor beta subunit has two subtypes of 95 kDa and 105 kDa. On the other hand, insulin receptor beta subunit is a separate single 95-kDa protein. Enzymatic digestion of IGF-I receptor beta subunit subtypes by glycopeptidase F resulted in similar molecular masses (84 kDa and 86 kDa) on SDS-PAGE, which suggests that the difference in molecular masses between two subtypes is attributable to the differences in N-linked complex-type carbohydrate chains on the extracellular domain of beta subunits. This conclusion is further supported by peptides of similar molecular mass following staphylococcal V8 protease digestion. Analysis of IGF-I receptor beta subunit subtypes in these cells may provide insights into the mechanism of action of IGF-I on neural tissues.
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PMID:Insulin-like growth factor I receptors on mouse neuroblastoma cells. Two beta subunits are derived from differences in glycosylation. 296 5

Human insulin-like growth factor I and II (IGF-I and IGF-II) in concentrations of 1-30 ng/ml, were shown to stimulate ornithine decarboxylase activity and [3H]thymidine incorporation in human SH-SY5Y neuroblastoma cells. Proliferation of these cells was also stimulated by IGF-I and II when added to RPMI 1640 medium, fortified with selenium, hydrocortisone, transferrin, and beta-estradiol. Labeled IGF-I and II bound to SH-SY5Y cells. The cross-reaction pattern of IGF-I, IGF-II, and insulin in competing with the binding of labeled IGF-I and IGF-II, respectively, indicated that SH-SY5Y cells express both type I and type II IGF receptors. Treatment of SH-SY5Y cells for 4 d with 12-O-tetradecanoylphorbol-13-acetate (TPA), which resulted in morphological and functional differentiation and growth inhibition, abolished the mitogenic response to both IGF-I and II. Concomitantly, the binding of IGF-II disappeared almost totally, which offers a possible explanation for the reduced biological response to IGF-II after TPA treatment. In contrast, the IGF-I binding in TPA-treated cells was only reduced to approximately 70% of the binding to control cells. It is therefore not excluded that the IGF-I receptor could be uncoupled by TPA, with persistent binding capacity for IGF-I.
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PMID:Mitogenic response of human SH-SY5Y neuroblastoma cells to insulin-like growth factor I and II is dependent on the stage of differentiation. 300 92

Insulin-like growth factors (IGF-I and IGF-II) are mitogenic polypeptides expressed in both developing and adult tissues. To examine the effects of IGFs on neuronal growth, we used SH-SY5Y neuroblastoma cells as an in vitro model of nervous system development. In the current study, we found that either IGF-I (0.1 to 10 nM), insulin (0.1 to 5 micrograms/ml) or calf serum (0.1 to 3%) increased SH-SY5Y proliferation over a 3 day period in a dose dependent manner. In each case, treatment with anti-IGF-I receptor antibodies blocked cell proliferation. IGF-II mRNA levels correlated with SH-SY5Y cell density; subconfluent cells expressed high levels of IGF-II mRNA while low levels of IGF-II mRNA were present in confluent cells. Similarly, serum deprivation increased IGF-I receptor mRNA by 4-fold. Collectively, these results support the concept that an IGF/IGF-I receptor system at least partially mediates SH-SY5Y cell proliferation and suggests the importance of IGFs in regulating neuronal growth.
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PMID:Effects of serum and insulin-like growth factors on human neuroblastoma cell growth. 826 10

Human non-autocrine neuroblastoma cells SK-N-SH and LF require serum for proliferation in vitro. We wished to determine the role of serum-borne insulin-like growth factor I (IGF-I) as mitogen for these cells. Introduction of the monoclonal antibody alpha-IR3 against human IGF-I receptor reduced proliferation in the presence of fetal bovine serum (FBS). IGF-I (5 nM) was as effective as FBS (10%) in stimulating proliferation. Porcine insulin mimicked the effects of IGF-I, but at a 1000-fold higher concentration. The antibody alpha-IR3 reduced growth stimulated by IGF-I more effectively than growth stimulated by insulin. Thus, proliferation of human non-autocrine neuroblastoma cells can be effectively manipulated by exogenous IGF-I.
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PMID:Insulin-like growth factor-I is a serum component stimulating growth of human neuroblastoma. 831 33

In the current studies, we examined whether focal adhesion kinase (FAK) and paxillin play a role in insulin-like growth factor-I (IGF-I)-stimulated morphological changes in neuronal cells. In SH-SY5Y human neuroblastoma cells, 10 nM IGF-I enhanced the extension of lamellipodia within 30 min. Scanning electron microscopy and staining with rhodamine-phalloidin showed that these lamellipodia displayed ruffles, filopodia, and a distinct meshwork of actin filaments. Immunofluorescent staining identified focal concentrations of FAK, paxillin, and phosphotyrosine within the lamellipodia. Immunoprecipitation experiments revealed that FAK and paxillin are tyrosine-phosphorylated during IGF-I-stimulated lamellipodial extension. Maximal phosphorylation of FAK and paxillin was observed 15-30 min after the addition of 10 nM IGF-I, whereas maximal IGF-I receptor phosphorylation occurred within 5 min. FAK, paxillin, and IGF-I receptor tyrosine phosphorylation had similar concentration-response curves and were inhibited by the receptor blocking antibody alphaIR-3. These results indicate that FAK and paxillin are tyrosine-phosphorylated during IGF-I-stimulated lamellipodial advance and suggest that the tyrosine phosphorylation of these two proteins helps mediate IGF-I-stimulated cell and growth cone motility. These responses contrast directly with recent reports showing insulin-stimulated dephosphorylation of FAK and paxillin.
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PMID:Tyrosine phosphorylation of paxillin and focal adhesion kinase during insulin-like growth factor-I-stimulated lamellipodial advance. 903 May 91


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