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

PURPOSE: To elucidate the thermal impact on biological processes the first three hours after hyperthermia (HT).

MATERIALS AND

METHODS

Tumor samples from BT(4)An 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 degrees 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.