Affiliations: Department of Neurosurgery, First Hospital of China Medical University, Liaoning, P. R. China | Department of Neurosurgery, University of Minnesota Medical School, Minneapolis, MN, USA
Note: [] Corresponding author: Anhua Wu, MD, PhD, Department of Neurosurgery, First Hospital of China Medical University, No.155, North Nanjing Street, Heping District, Shenyang, Liaoning, 110001 P. R. China. Tel.: 86 24 23517483; Fax: 86 24 23517819; E-mail: [email protected].
Abstract: Background: IL-13Ra2 is overexpressed by gliomas but not by normal tissue. However, the molecular basis for IL-13Ra2 overexpression in gliomas is unknown. Methods: In the present study we have investigated the regulatory mechanisms that are responsible for the expression of IL-13Ra2 with mutation analysis, quantitative RT-PCR, Flow cytometry analysis, transcription factor binding assay and Elisa. Results: Our results reveal a complex mechanism for regulating IL-13Ra2 expression that involves at least 2 promoters and 4 transcripts of human IL-13Ra2. Transcription factors NFAT and AP1 are necessary and essential for the expression of this GBM related transcript, and are responsible for the high level of expression of IL-13Ra2 in GBM. Most interestingly, we found that expression of this transcript results in the production of a secreted form of IL-13Ra2 and thus may have the potential to be used as a diagnostic biomarker for GBM patients and other cancer patients that express the soluble form of this receptor. Conclusion: This study is the first to characterize the role of NFAT and AP1 in the regulation of IL-13Ra2 expression, and provides insight into understanding the high levels of IL-13Ra2 expressed by GBM cells.
