TPA-mediated regulation of osteopontin in human malignant glioma cells.

Academic Article

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.
  • Published In

    Keywords

  • Calcium, Glioma, Humans, Osteopontin, Protein Kinase C, RNA, Messenger, Sialoglycoproteins, Tetradecanoylphorbol Acetate, Tumor Cells, Cultured
  • Author List

  • Tucker MA; Chang PL; Prince CW; Gillespie GY; Mapstone TB
  • Start Page

  • 807
  • End Page

  • 812
  • Volume

  • 18
  • Issue

  • 2A