Overexpression of bax in human glioma cell lines

Michael A. Vogelbaum, Jianxin X. Tong, Rajashri Perugu, David H. Gutmann, Keith M. Rich

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

Object. Cells that lose their ability to undergo apoptosis may promote the development of neoplasms and result in resistance to clinical treatment with DNA-damaging modalities such as radio- and chemotherapy. Four established human glioma cell lines that are resistant to apoptosis were transfected with the proapoptotic gene bax and assessed for their sensitivity to a proapoptotic stimulus. Methods. Two cell lines had a wild-type p53 genotype (U87 and D247MG) and two had mutant p53 genotypes (U138 and U373). Constitutive overexpression of murine bax was achieved in U138 and U373 only, which resulted in an increased sensitivity of these lines to the apoptosis- inducing effect of cytosine arabinoside (ara-C). Multiple attempts to produce constitutive overexpression of bax in U87 and D247MG cells resulted in spontaneous, near-complete cell loss. Vector-only control transfections were successful in all four cell lines. Inducible overexpression of bax was achieved in the U87 cells and elevated levels of BAX were observed as early as 6 hours after gene induction. This overexpression of BAX resulted in the spontaneous induction of apoptosis in these cells. Conclusions. Overexpression of BAX in four human glioma cell lines resulted in increased sensitivity to apoptosis. In the two lines that had a wild-type p53 genotype, overexpression of BAX produced spontaneous apoptosis. In contrast, the lines that had mutant, nonfunctional P53 did not undergo spontaneous apoptosis, but they were rendered more sensitive to the apoptosis-inducing effect of ara-C. Modulation of BAX expression may be a useful therapeutic modality for gliomas, regardless of p53 genotype.

Original languageEnglish
Pages (from-to)483-489
Number of pages7
JournalJournal of neurosurgery
Volume91
Issue number3
DOIs
StatePublished - Sep 1999

Keywords

  • Apoptosis
  • Bcl-2 gene family
  • Brain neoplasm
  • Chemotherapy
  • Gene therapy
  • P53 gene

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