Global gene expression analyses reveal changes in biological processes after hyperthermia in a rat glioma model

Abstract

Purpose: To elucidate the thermal impact on biological processes the first three hours after hyperthermia (HT).Materials and methods: Tumor samples from BT4An rat tumors were transplanted subcutaneously to the right hind foot of BD IX rats, treated with local water-bath HT (mean tumor temperature of 43°C) for one hour, and analyzed for changes in global gene expression the first three hours after treatment with HT. Samples from a corresponding in vitro experiment were also analyzed. Differentially expressed genes in vivo were mapped to a gene ontology (GO) database in search for biological processes overrepresented after treatment with HT. Selected genes were verified using Taqman quantitative RT-PCR.Results: 1213 genes were differentially expressed after HT treatment in vivo. Processes overrepresented by GO mapping could be sorted into 10 main functional groups; apoptosis, transcription, immune system, blood vessels, metabolism/protein modifications, differentiation, cell signaling, response to stimulus, transport and cytoskeleton. We detected reduced mRNA levels of a wide range of T-cell, natural killer cell and antigen presenting cell-related genes after HT.Conclusion: To our best knowledge, this is the first global microarray analysis of a malignant tumor treated with HT in vivo. We highlight biological processes affected by HT. RNA expression profiles also indicate a rapid suppression of the immune system within tumors by local HT.