Somatostatin receptors in gliomas.
Gliomas differ from non-malignant glial cells in the overexpression or mutations of genes involved in cell cycle or growth regulation. One example is the overexpression of the somatostatin receptor subtype 2 (sst2), especially of the splice variant sst2A. The reasons for this overexpression are not known. However, the coding sequence and part of the promoter region is not mutated. In accordance to this, the sst2 is functionally active and is internalised upon agonist stimulation. Immunoelectronmicroscopic studies show that the activated sst2 is internalised via caveolin-positive endosomal vesicles and later accumulates in multivesicular bodies and lysosomal compartments. The activated sst2 is found to be co-localised with the inhibitory G-protein Gialpha at the plasma membrane and in early endosomal vesicles. Multiple signal transduction pathways are induced. Stimulation of sst2 lowers cAMP levels elicited by forskolin and activates the protein tyrosine phosphatase SHP-2. In contrast to other sst2-expressing cells a long term antiproliferative effect of somatostatin or sst2-selective agonists are not detected in cultivated glioma cells. However, continuous stimulation of sst2 decreases the expression of genes promoting tumour survival.
Held-Feindt
J
J
Department of Anatomy, University of Kiel, Germany. held-feindt@anat.uni-kiel.de
Krisch
B
B
Forstreuter
F
F
Mentlein
R
R
D000595:Amino Acid Sequence; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D017481:Receptors, Somatostatin / Q000235:genetics* / Q000378:metabolism
D017481:Receptors, Somatostatin; C093733:somatostatin receptor 2