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NFAT and AP1 are essential for the expression of a glioblastoma multiforme related IL-13Ra2 transcript
Anhua Wu1, Katya Ericson, Wang Chao
1Department of Neurosurgery, First Hospital of China Medical University, Liaoning, P. R. China. wuanhua@yahoo.com
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.
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