Scientific Publications by FDA Staff

J Neurooncol 2005 Mar;72(1):35-46

Analysis of target genes induced by IL-13 cytotoxin in human glioblastoma cells.

Han J, Yang L, Puri RK

Puri RK, NIH, CBER, FDA, Ctr Informat Technol,Bioinformat & Mol Anal Sect, Bldg 29B,Rm 2NN10,29 Lincoln Dr, Bethesda, MD 20892 USA NIH, CBER, FDA, Ctr Informat Technol,Bioinformat & Mol Anal Sect, Bethesda, MD 20892 USA US FDA, Ctr Biol Evaluat & Res, Lab Mol Tumor Biol, CBER,NCI Genom Program,Div Cellular & Gene Therap, Bethesda, MD USA

IL-13 cytotoxin comprised of IL-13 and a mutated form of Pseudomonas exotoxin (fusion protein termed IL-13-PE38QQR) has been shown to inhibit protein synthesis leading to necrotic and apoptotic cell death in glioblastoma cells that express high levels of interleukin-13 receptors (IL-13R). To identify target genes of cell death and other cellular genes with IL-13 receptors in glioblastoma cells, we utilized the cDNA microarrays to analyze global gene expression profiles after IL-13 cytotoxin and IL-13 treatment. IL-13 cytotoxin mediated cytotoxicity to U251 cells in a dose-dependant manner. Hierarchical cluster analysis of differentially expressed genes in U251 glioma cells at different time points after IL-13 cytotoxin treatment showed three major groups, each representing a specific expression pattern. Randomly selected differentially expressed genes from each group were confirmed by RT-PCR analysis. Most down-regulated genes belong to cell adhesion, motility, angiogenesis, DNA repair, and metabolic pathways. While up-regulated genes belong to cell cycle arrest, apoptosis, signaling and various metabolic pathways. Unexpectedly, at early time points, both IL-13 and IL-13 cytotoxin induced several genes belonging to different pathways most notably IL-8, DIO2, END1, and ALDH1A3 indicating that these genes are early response genes and their products may be associated with IL-13R. In addition, IL-13 cytotoxin induced IL-13Ralpha2 mRNA expression during the treatment in glioma cells. Our results indicate that novel cellular genes are involved with IL-13 receptors and that IL-13 cytotoxin induced cell death involves various target genes in human glioblastoma cells. On going studies will determine the role of associated genes and their products in the IL-13R functions in glioma cells.