title: TPA-mediated regulation of osteopontin in human malignant glioma cells.
abstract: Malignant gliomas are the most common primary intracranial neoplasms in adults and are largely refractory to post-surgical therapy despite intensive therapeutic efforts. Using a number of different brain tumor-derived cell lines we have demonstrated that the mRNA for osteopontin (OPN), which is substantially over-expressed by some tumors in comparison with normal tissues, is preferentially expressed in high grade and metastatic brain tumors compared to low grade brain tumors. One glioma-derived cell line, U105MG, which does not express significant amounts of OPN mRNA, could be induced dose-dependently by the tumor-promoting and PKC-activating phorbol ester, TPA, to over-express OPN mRNA in a PKC-dependent manner. Unexpectedly, treatment of U105MG cells with Ca2+ ionophore (A23187) completely inhibited TPA-mediated induction of OPN while treatment with the intracellular Ca2+ antagonist TMB-8 had no significant effect. Elucidation of regulatory mechanisms for OPN induction in glioma cells should facilitate rational design of novel therapeutics for human malignant gliomas.
authors.affiliation: Department of Nutrition Sciences, University of Alabama at Birmingham 35294, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Tucker
authors.forename: P L
authors.initials: PL
authors.lastname: Chang
authors.forename: C W
authors.initials: CW
authors.lastname: Prince
authors.forename: G Y
authors.initials: GY
authors.lastname: Gillespie
authors.forename: T B
authors.initials: TB
authors.lastname: Mapstone
mesh_terms: D002118:Calcium / Q000378:metabolism; D005910:Glioma / Q000378:metabolism*; D006801:Humans; D053495:Osteopontin; D011493:Protein Kinase C / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D012795:Sialoglycoproteins / Q000032:analysis* / Q000235:genetics; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D012333:RNA, Messenger; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; D053495:Osteopontin; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium