The Gem GTP-binding protein promotes morphological differentiation in neuroblastoma.
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.
Leone
A
A
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.
Mitsiades
N
N
Ward
Y
Y
Spinelli
B
B
Poulaki
V
V
Tsokos
M
M
Kelly
K
K
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002454:Cell Differentiation; D018679:Cholinergic Agonists / Q000494:pharmacology; D018305:Ganglioneuroblastoma / Q000473:pathology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D008545:Melanoma / Q000473:pathology; D051379:Mice; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D009447:Neuroblastoma / Q000473:pathology*; D011976:Receptors, Muscarinic / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D012668:Trigeminal Ganglion / Q000737:chemistry; D014407:Tumor Cells, Cultured
D018679:Cholinergic Agonists; D017874:Immediate-Early Proteins; D009363:Neoplasm Proteins; D011976:Receptors, Muscarinic; D002217:Carbachol; C490245:GEM protein, human; C088119:Gem protein, mouse; D020559:Monomeric GTP-Binding Proteins; D013755:Tetradecanoylphorbol Acetate