Transfection of IFNalpha in human glioblastoma cells and tumorigenicity in association with induction of PKR and OAS gene expression.
Previously these authors and others demonstrated frequent homozygous deletions of the chromosome 9p-localized class I interferon (IFN) gene cluster in glioblastoma tumors 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 IFNalpha "transfectant" of the cell line U118. The expression of IFNalpha 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 IFNalpha 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 IFNalpha transfectants. These results indicate a differential responsiveness among these four genes to constitutive IFNalpha expression, and suggest that the suppression of U118-transformed phenotypes by IFNalpha transfection may be mediated by the induction of specific IFN response genes thought to have a negative growth-regulatory function.
He
J
J
Department of Neurosurgery, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Olson
J J
JJ
Ekstrand
A J
AJ
Serbanescu
A
A
Yang
J
J
Offermann
M K
MK
James
C D
CD
D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics*; D001483:Base Sequence; D001932:Brain Neoplasms / Q000235:genetics*; D017353:Gene Deletion; D015870:Gene Expression; D005909:Glioblastoma / Q000235:genetics*; D006801:Humans; D016898:Interferon-alpha / Q000235:genetics*; D008969:Molecular Sequence Data; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D019892:eIF-2 Kinase
D016898:Interferon-alpha; D012333:RNA, Messenger; D017346:Protein Serine-Threonine Kinases; D019892:eIF-2 Kinase; D015088:2',5'-Oligoadenylate Synthetase