Influence of the somatostatin receptor sst2 on growth factor signal cascades in human glioma cells.

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.

• Authors: J Held-Feindt, F Forstreuter, T Pufe, R Mentlein
• Journal: Brain research. Molecular brain research (Brain Res Mol Brain Res) Vol. 87 Issue 1 Pg. 12-21 (Feb 19 2001) ISSN: 0169-328X [Print] Netherlands
• PMID: 11223155 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Benzimidazoles
• Hormones
• Indoles
• Intracellular Signaling Peptides and Proteins
• L 054522
• Proto-Oncogene Proteins c-jun
• Receptors, Somatostatin
• Transcription Factor AP-1
• Somatostatin
• somatostatin receptor 2
• ErbB Receptors
• Receptors, Platelet-Derived Growth Factor
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3
• Mitogen-Activated Protein Kinases
• PTPN6 protein, human
• Protein Tyrosine Phosphatase, Non-Receptor Type 6
• Protein Tyrosine Phosphatases
• Octreotide

Topics

• Benzimidazoles (pharmacology)
• Brain Neoplasms
• Cell Division (drug effects, physiology)
• ErbB Receptors (metabolism)
• Gene Expression Regulation, Neoplastic
• Glioma
• Hormones (pharmacology)
• Humans
• Indoles (pharmacology)
• Intracellular Signaling Peptides and Proteins
• MAP Kinase Signaling System (physiology)
• Mitogen-Activated Protein Kinase 1 (metabolism)
• Mitogen-Activated Protein Kinase 3
• Mitogen-Activated Protein Kinases (metabolism)
• Octreotide (pharmacology)
• Phosphorylation
• Protein Tyrosine Phosphatase, Non-Receptor Type 6
• Protein Tyrosine Phosphatases (metabolism)
• Proto-Oncogene Proteins c-jun (genetics)
• Receptors, Platelet-Derived Growth Factor (metabolism)
• Receptors, Somatostatin (genetics, metabolism)
• Somatostatin (pharmacology)
• Transcription Factor AP-1 (metabolism)
• Tumor Cells, Cultured