Held-Feindt J, Forstreuter F, Pufe T, Mentlein R
Department of Anatomy, University of Kiel, Olshausenstrasse 40, D-24098, Kiel, Germany.
Brain Res Mol Brain Res. 2001 Feb 19;87(1):12-21. doi: 10.1016/s0169-328x(00)00225-4.
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.
生长抑素受体亚型sst2A在胶质瘤中高表达、无突变且功能活跃。用生长抑素、奥曲肽（sst2、sst3和sst5选择性肽激动剂）或sst2选择性非肽激动剂L-054,522刺激培养的人U343胶质瘤细胞后，可诱导多种信号转导途径：升高的cAMP水平降低，蛋白酪氨酸磷酸酶（尤其是SHP2）被激活，丝裂原活化蛋白激酶被抑制。磷酸酶的刺激导致表皮生长因子（EGF）和血小板衍生生长因子（PDGF）的活化受体去磷酸化，因此在共刺激实验中，丝裂原活化蛋白激酶ERK 1和2（p42/p44）去磷酸化。此外，生长抑素或sst2选择性激动剂在转录和翻译水平上降低了EGF刺激的AP-1复合物（c-jun/c-jun）的表达。这些实验表明，刺激性和抑制性受体的相互作用是调节信号级联反应和基因表达的重要机制。
