Transfection of IFNα in human glioblastoma cells and tumorigenicity in association with induction of PKR and OAS gene expression

Ju He, Jeffrey J. Olson*, A. Jonas Ekstrand, Andrei Serbanescu, Jing Yang, Margaret K. Offermann, C. David James

*Corresponding author for this work

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Previously these authors and others demonstrated frequent homozygous deletions of the chromosome 9p-localized class I interferon (IFN) gene cluster in glioblastoma tumor and cell lines. To investigate the biological effects of class I IFN gene transfer and constitutive expression in glioblastoma cells devoid of this gene cluster, the authors have developed a stable IFNα 'transfectant' of the cell line U118. The expression of IFNα protein in the U118 transfectant clone is associated with decreased levels of DNA synthesis exhibited by cultures of transfected cells, reduced colony- forming ability in soft agar, and loss of tumorigenicity in athymic nude mice. To address the molecular consequences of constitutive IFNα synthesis, they examined the expression of four genes whose transcription has been shown to be responsive to IFN-mediated signal transduction and could be important to the observed antiproliferative and antitumor effects. Northern blot analysis revealed that changes in the levels of messenger (m)RNA for two of these genes, c-myc and mhc class I, are minor. However, mRNAs for oligoadenylate synthetase (OAS) as well as double-stranded RNA-activated protein kinase (PKR), which are not expressed in parental U118 cells, were constitutively expressed in IFNα transfectants. These results indicate a differential responsiveness among these four genes to constitutive IFNα expression, and suggests that the suppression of U118-transformed phenotypes by IFNα transfection may be mediated by the induction of specific IFN response genes thought to have a negative growth-regulatory function.

Original languageEnglish (US)
Pages (from-to)1085-1090
Number of pages6
JournalJournal of neurosurgery
Volume85
Issue number6
DOIs
StatePublished - Dec 1996

Keywords

  • constitutive expression
  • gene deletion
  • signal transduction

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology

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