Issue (if applicable)
INTRODUCTION: Human cytomegalovirus (HCMV) DNA and protein are found in gliomas but not in normal brain or other primary brain tumors. The role of HCMV infection in glioma biology is unclear. While it is unlikely that HCMV infection causes glioma, viral proteins might impart a proliferative and antiapoptotic phenotype that confers a survival advantage. Does this oncomodulation translate into a clinically relevant effect in glioma cells? To answer this question, we compared the response of the U87IE1 and U87MG malignant glioma cell lines to temozolomide. U87IE1 cells are U87MG cells that have been genetically engineered to produce HCMV IE1 protein. (The U87IE1 cell line is a generous gift from Charles Cobbs.) METHODS: Approximately 5,000 U87IE1 and U87MG cells in normal culture media were placed into wells of a 96-well plate. After 24 hours, the media was replaced with culture media containing temozolomide in increasing concentration. After 48 hours, cell viability was assessed using a luminescent assay. A dose-response curve for each cell line was generated using statistical software. The concentration of temozolomide resulting in 50% of cell death (the EC50 value) for each cell line was determined. Results: The EC50 for temozolomide in the U87MG cell line is 565.6 micromolar, while in the U87IE1 cell line it is 1319 micromolar. This difference is statistically significant (p < 0.0001) and indicates that the U87IE1 cells are more resistant to temozlomide than are the U87MG cells. CONCLUSION: HCMV IE1 expression by U87MG cells enhances their proliferation and survival. In this study, we show that this oncomodulatory effect is clinically relevant: the U87IE1 cell line is more resistant than the U87MG cell line to temozolomide. This finding suggests that HCMV is a viable treatment target for patients with glioma.
Richard A. Rovin, Johnathan E. Lawrence, Justin J. Segula, and Robert J. Winn. "Expression of HCMV IE1 in the U87MG Cell Line Augments Resistance to Temozolomide" Neuro-Oncology 12.suppl 4 (2010): iv7-iv25. Available at: http://works.bepress.com/johnathan_lawrence/8