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      Dexamethasone blocks the migration of the human neuroblastoma cell line SK-N-SH

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          Abstract

          Glucocorticoids (Gc) influence the differentiation of neural crest-derived cells such as those composing sympathoadrenal tumors like pheochromocytomas, as well as neuroblastomas and gangliomas. In order to obtain further information on the effects of Gc on cells evolving from the neural crest, we have used the human neuroblastoma cell line SK-N-SH to analyze: 1) the presence and the binding characteristics of Gc receptors in these cells, 2) the effect of dexamethasone (Dex) on the migration of SK-N-SH cells, and 3) the effect of Dex on the organization of the cytoskeleton of SK-N-SH cells. We show that: 1) receptors that bind [³H]-Dex with high affinity and high capacity (Kd of 9.6 nM, Bmax of 47 fmol/mg cytosolic protein, corresponding to 28,303 sites/cell) are present in cytosolic preparations of SK-N-SH cells, and 2) treatment with Dex (in the range of 10 nM to 1 µM) has an inhibitory effect (from 100% to 74 and 43%, respectively) on the chemotaxis of SK-N-SH cells elicited by fetal bovine serum. This inhibition is completely reversed by the Gc receptor antagonist RU486 (1 µM), and 3) as demonstrated by fluorescent phalloidin-actin detection, the effect of Dex (100 nM) on SK-N-SH cell migration is accompanied by modifications of the cytoskeleton organization that appear with stress fibers. These modifications did not take place in the presence of 1 µM RU486. The present data demonstrate for the first time that Dex affects the migration of neuroblastoma cells as well as their cytoskeleton organization by interacting with specific receptors. These findings provide new insights on the mechanism(s) of action of Gc on cells originating in the neural crest.

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          Most cited references41

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          A Rapid and Sensitive Method for the Quantitation of Microgram Quantities of Protein Utilizing the Principle of Protein-Dye Binding

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            Ligand: a versatile computerized approach for characterization of ligand-binding systems.

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              Rho GTPases and the actin cytoskeleton.

              A. Hall (1998)
              The actin cytoskeleton mediates a variety of essential biological functions in all eukaryotic cells. In addition to providing a structural framework around which cell shape and polarity are defined, its dynamic properties provide the driving force for cells to move and to divide. Understanding the biochemical mechanisms that control the organization of actin is thus a major goal of contemporary cell biology, with implications for health and disease. Members of the Rho family of small guanosine triphosphatases have emerged as key regulators of the actin cytoskeleton, and furthermore, through their interaction with multiple target proteins, they ensure coordinated control of other cellular activities such as gene transcription and adhesion.
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                Author and article information

                Journal
                bjmbr
                Brazilian Journal of Medical and Biological Research
                Braz J Med Biol Res
                Associação Brasileira de Divulgação Científica (Ribeirão Preto, SP, Brazil )
                0100-879X
                1414-431X
                September 2006
                : 39
                : 9
                : 1233-1240
                Affiliations
                [01] Brasília DF orgnameEscola Superior em Ciências da Saúde Brasil
                [02] Milano orgnameUniversity of Milano orgdiv1Center of Endocrinological Oncology orgdiv2Department of Endocrinology Italy
                [03] Wroclaw orgnameWroclaw Medical University orgdiv1Department of Endocrinology and Diabetology Poland
                Article
                S0100-879X2006000900011 S0100-879X(06)03900911
                0bf4a848-3df7-46e4-aa6f-45b733af6654

                This work is licensed under a Creative Commons Attribution 4.0 International License.

                History
                : 29 May 2006
                : 11 July 2005
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 40, Pages: 8
                Product

                SciELO Brazil

                Categories
                Neurosciences and Behavior

                Glucocorticoids,Cytoskeleton,Migration,SK-N-SH cells,Human neuroblastoma

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