TPA-mediated regulation of osteopontin in human malignant glioma cells.
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.
Tucker
M A
MA
Department of Nutrition Sciences, University of Alabama at Birmingham 35294, USA.
Chang
P L
PL
Prince
C W
CW
Gillespie
G Y
GY
Mapstone
T B
TB
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
D012333:RNA, Messenger; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; D053495:Osteopontin; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium