RBIO-06. CROSSTALK OF ErbB2 WITH LEF1 REGULATES JAGGED1-MEDIATED RADIORESISTANCE IN GLIOBLASTOMA

ErbB2 (Her2) belongs to the family of EGF receptor tyrosine kinases and plays a vital oncogenic role in several cancers. Gliomas are reported to have aberrant overexpression of ErbB2, but its role in glioma biology and treatment resistance have not been well studied. We have previously reported that ionizing radiation (IR) increases cell invasiveness and radioresistance. In our preliminary studies, we observed that shRNA mediated ErbB2 silencing in glioma cell lines resulted in a significant inhibition of proliferation and invasion which was associated with a suppression of Notch signaling. To examine its role in radioresistance, we treated glioma cells with IR and observed that the cells exhibited a significant increase in invasiveness associated with nuclear translocation of ErbB2 and transcriptional upregulation of the Notch receptor ligand, Jagged-1. To further investigate the relationship between ErbB2 translocation and Notch signaling, we performed immunoprecipitation and transcription factor binding array studies in IR-treated cells which revealed an interesting association of nuclear ErbB2 with the TCF1/LEF1 complex that is known to transcriptionally regulate Jagged-1 expression. In addition, chromatin-binding assays showed recruitment of ErbB2 to putative LEF1 consensus sites of the Jagged-1 promoter, suggesting a potential role for ErbB2 in the transcriptional regulation of Jagged-1 and consequently of Notch signaling after radiation in glioma cells. Further, downre...
Source: Neuro-Oncology - Category: Cancer & Oncology Authors: Tags: RADIOBIOLOGY Source Type: research