title: Immediate early gene IEX-1 induces astrocytic differentiation of U87-MG human glioma cells.
abstract: The immediate early response gene IEX-1 is involved in the regulation of apoptosis and cell growth. In order to increase the apoptotic sensitivity to chemotherapeutic drugs and gamma-ray, we attempted to establish U87-MG human glioma cell line expressing IEX-1. Unexpectedly, however, transfection of IEX-1 into U87-MG glioma cells resulted in morphological changes to astrocytic phenotype and increase in glial differentiation marker proteins, S-100 and glial fibrillary acidic protein (GFAP). Glial cell differentiation was used to examine in rat C6 glioma cell line, since this cell line express astrocytic phenotypes by increase in intracellular cAMP concentration. Stimulation of human U87-MG glioma cells by membrane-permeable dibutyryl cAMP (dbcAMP) not only elicited their morphological changes but also induced expression of IEX-1 as well as S-100 and GFAP. H89, an inhibitor of protein kinase A (PKA), blocked dbcAMP-induced morphological changes of U87-MG cells and expression of IEX-1. In contrast, morphological changes and expression of S-100 and GFAP induced by IEX-1 were not affected by H89. Morphological changes induced by dbcAMP were totally abolished by functional disruption of IEX-1 expression by anti-sense RNA. These results indicate that IEX-1 plays an important role in astrocytic differentiation of human glioma cells and that IEX-1 functions at downstream of PKA.
authors.affiliation: Department of Cell Signaling, Division of Cell and Molecular Biology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan.
authors.forename: Fukka
authors.initials: F
authors.lastname: You
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Osawa
authors.forename: Shin-ichiro
authors.initials: S
authors.lastname: Hayashi
authors.forename: Shigeru
authors.initials: S
authors.lastname: Nakashima
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis / Q000502:physiology*; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D003563:Cyclic CMP / Q000031:analogs & derivatives / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D008565:Membrane Proteins / Q000096:biosynthesis / Q000502:physiology*; D051381:Rats; D009418:S100 Proteins / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D051017:Apoptosis Regulatory Proteins; D005904:Glial Fibrillary Acidic Protein; C099815:IER3 protein, human; D007546:Isoquinolines; D008565:Membrane Proteins; D009418:S100 Proteins; D013449:Sulfonamides; D003563:Cyclic CMP; C053441:dibutyryl cyclic-3',5'-cytidine monophosphate; D017868:Cyclic AMP-Dependent Protein Kinases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide