Leone A, Mitsiades N, Ward Y, Spinelli B, Poulaki V, Tsokos M, Kelly K
Cell and Cancer Biology Department, Medicine Branch, Division of Clinical Sciences, National Cancer Institute, Building 10, Room 3B43, 9000, Rockville Pike, Bethesda, Maryland, MD 20892, USA.
Oncogene. 2001 May 31;20(25):3217-25. doi: 10.1038/sj.onc.1204420.
Gem is a small GTP-binding protein within the Ras superfamily whose function has not been determined. We report here that ectopic Gem expression is sufficient to stimulate cell flattening and neurite extension in N1E-115 and SH-SY5Y neuroblastoma cells, suggesting a role for Gem in cytoskeletal rearrangement and/or morphological differentiation of neurons. Consistent with this potential function, in clinical samples of neuroblastoma, Gem protein was most highly expressed within cells which had differentiated to express ganglionic morphology. Gem was also observed in developing trigeminal nerve ganglia in 12.5 day mouse embryos, demonstrating that Gem expression is a property of normal ganglionic development. Although Gem expression is rare in epithelial and hematopoietic cancer cell lines, constitutive Gem levels were detected in several neuroblastoma cell lines and could be further induced as much as 10-fold following treatment with PMA or the acetylcholine muscarinic agonist, carbachol.
Gem是Ras超家族中的一种小GTP结合蛋白，其功能尚未确定。我们在此报告，异位表达Gem足以刺激N1E-115和SH-SY5Y神经母细胞瘤细胞的细胞扁平化和神经突延伸，这表明Gem在神经元的细胞骨架重排和/或形态分化中发挥作用。与这种潜在功能一致的是，在神经母细胞瘤的临床样本中，Gem蛋白在已分化为表达神经节形态的细胞中表达最高。在12.5天的小鼠胚胎发育中的三叉神经节中也观察到了Gem，这表明Gem的表达是正常神经节发育的一个特性。虽然Gem在上皮和造血癌细胞系中很少表达，但在几种神经母细胞瘤细胞系中检测到了组成型Gem水平，在用佛波酯（PMA）或乙酰胆碱毒蕈碱激动剂卡巴胆碱处理后，其水平可进一步诱导高达十倍。
