Orthotopic growth of human glioma cells quantitatively and qualitatively influences radiation-induced changes in gene expression.
The effect of radiation on gene expression has been most frequently studied using tissue culture models. To determine the influence of experimental growth condition on radiation-induced changes in gene expression, microarray analysis was done on two human glioma cell lines (U87 and U251) grown in tissue culture and as s.c. or i.c. xenografts. Compared with tissue culture, the number of genes, whose expression was affected by radiation in both cell lines, was increased in the s.c. xenografts and further increased in the orthotopic tumors. Furthermore, in each growth condition, radiation modulated the expression of a different set of genes. In addition, whereas there were few commonly affected genes after irradiation of U87 and U251 in tissue culture, there were 729 common changes after orthotopic irradiation. These results indicate that the influence of the orthotopic environment on radiation-induced modulation of gene expression in glioma cells was both quantitative and qualitative. Moreover, they suggest that investigations of the functional consequence of radiation-induced gene expression will require accounting for experimental growth conditions.
Camphausen
Kevin
K
Radiation Oncology Branch, National Cancer Institute and National Institutes of Neurological Disorder and Stroke, Bethesda, Maryland 20892, USA. camphauk@mail.nih.gov
Purow
Benjamin
B
Sproull
Mary
M
Scott
Tamalee
T
Ozawa
Tomoko
T
Deen
Dennis F
DF
Tofilon
Philip J
PJ
D000818:Animals; D048708:Cell Growth Processes / Q000235:genetics / Q000528:radiation effects; D045744:Cell Line, Tumor; D015870:Gene Expression / Q000528:radiation effects*; D005910:Glioma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D051379:Mice; D009368:Neoplasm Transplantation; D020411:Oligonucleotide Array Sequence Analysis; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured