Abstract
The somatostatin receptor subtype sst2A is highly expressed, non-mutated and functionally active in gliomas. After stimulation of cultivated human U343 glioma cells with somatostatin, octreotide (sst2-, sst3- and sst5-selective peptide agonist) or the sst2-selective non-peptide agonist L-054,522 multiple signal transduction pathways are induced: elevated cAMP levels are reduced, protein tyrosine phosphatases (especially SHP2) are activated and mitogen-activated protein kinases are inhibited. Stimulation of the phosphatases resulted in dephosphorylation of activated receptors for EGF and PDGF (epidermal and platelet-derived growth factor), and as a consequence the mitogen-activated protein kinases ERK 1 and 2 (p42/p44) were de-phosphorylated in co-stimulation experiments. Furthermore, somatostatin or sst2-selective agonists reduced EGF-stimulated expression of the AP-1 complex (c-jun/c-jun) on the transcriptional and translational level. These experiments show that the interaction of stimulatory and inhibitory receptors are important mechanisms for the regulation of signal cascades and gene expression.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Benzimidazoles / pharmacology
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Brain Neoplasms*
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Cell Division / drug effects
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Cell Division / physiology
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ErbB Receptors / metabolism
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Gene Expression Regulation, Neoplastic
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Glioma*
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Hormones / pharmacology
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Humans
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Indoles / pharmacology
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Intracellular Signaling Peptides and Proteins
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MAP Kinase Signaling System / physiology
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Mitogen-Activated Protein Kinase 1 / metabolism
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases / metabolism
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Octreotide / pharmacology
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Phosphorylation
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Protein Tyrosine Phosphatase, Non-Receptor Type 6
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Protein Tyrosine Phosphatases / metabolism
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Proto-Oncogene Proteins c-jun / genetics
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Receptors, Platelet-Derived Growth Factor / metabolism
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Receptors, Somatostatin / genetics*
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Receptors, Somatostatin / metabolism*
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Somatostatin / pharmacology
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Transcription Factor AP-1 / metabolism
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Tumor Cells, Cultured
Substances
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Benzimidazoles
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Hormones
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Indoles
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Intracellular Signaling Peptides and Proteins
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L 054522
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Proto-Oncogene Proteins c-jun
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Receptors, Somatostatin
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Transcription Factor AP-1
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Somatostatin
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somatostatin receptor 2
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ErbB Receptors
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Receptors, Platelet-Derived Growth Factor
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases
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PTPN6 protein, human
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Protein Tyrosine Phosphatase, Non-Receptor Type 6
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Protein Tyrosine Phosphatases
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Octreotide