Held-Feindt J, Krisch B, Forstreuter F, Mentlein R
Department of Anatomy, University of Kiel, Germany.
J Physiol Paris. 2000 May-Aug;94(3-4):251-8. doi: 10.1016/s0928-4257(00)00213-8.
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.
胶质瘤与非恶性神经胶质细胞的不同之处在于，其参与细胞周期或生长调节的基因存在过表达或突变。一个例子是生长抑素受体2型（sst2）的过表达，尤其是剪接变体sst2A。这种过表达的原因尚不清楚。然而，其编码序列和部分启动子区域未发生突变。据此，sst2具有功能活性，并且在激动剂刺激后会发生内化。免疫电子显微镜研究表明，激活的sst2通过小窝蛋白阳性的内体囊泡内化，随后积聚在多囊泡体和溶酶体区室中。发现激活的sst2在质膜和早期内体囊泡中与抑制性G蛋白Gialpha共定位。诱导了多种信号转导途径。sst2的刺激降低了福斯高林引起的cAMP水平，并激活了蛋白酪氨酸磷酸酶SHP-2。与其他表达sst2的细胞不同，在培养的胶质瘤细胞中未检测到生长抑素或sst2选择性激动剂的长期抗增殖作用。然而，持续刺激sst2会降低促进肿瘤存活的基因的表达。
