Global gene expression analyses reveal changes in biological processes after hyperthermia in a rat glioma model.
OBJECTIVE
To elucidate the thermal impact on biological processes the first three hours after hyperthermia (HT).


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.


CONCLUSIONS
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.
Borkamo
Erling Dahl
ED
Section of Oncology, Institute of Medicine, University of Bergen, Bergen, Norway. erling.dahl@helse-bergen.no
Dahl
Olav
O
Bruland
Ove
O
Fluge
Oystein
O
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000503:physiopathology* / Q000628:therapy*; D006360:Heat-Shock Proteins / Q000378:metabolism; D006979:Hyperthermia, Induced; D007109:Immunity / Q000502:physiology; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000503:physiopathology / Q000628:therapy; D020411:Oligonucleotide Array Sequence Analysis; D011506:Proteins / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics
D006360:Heat-Shock Proteins; D011506:Proteins; D014157:Transcription Factors