Notch-1 regulates transcription of the epidermal growth factor receptor through p53
admin The Notch path plays a key persona in the utilization and is progressively constituted for its grandness in cancer. We demonstrated previously the overexpression of Notch-1 and its ligands in gliomas and showed that their collective inhibits glioma radiophone proliferation and survival. To explicate the mechanisms downstream of Notch-1 in glioma cells, we performed microarray profiling of glioma cells transfected with Notch-1 diminutive meddling RNA. Notable among downregulated transcripts was the stratum ontogeny bourgeois organ (EGFR), famous to be overexpressed or amplified in gliomas and striking in another cancers as well. Further studies addicted that Notch-1 action attenuated EGFR traveller polymer (mRNA) and EGFR accelerator in glioma and another radiophone lines. Transfection with Notch-1 accumulated EGFR expression. Additionally, we institute a momentous reciprocity in levels of EGFR and Notch-1 RNA in direct high-grade manlike gliomas. Subsequent experiments showed that p53, an activator of the EGFR promoter, is thermostated by Notch-1. Experiments with p53-positive and -null radiophone lines addicted that p53 part mediates the personalty of Notch-1 on EGFR expression. These results exhibit for the prototypal instance that Notch-1 upregulates EGFR countenance and also shew Notch-1 conception of p53 in gliomas. These observations hit momentous implications for discernment the mechanisms of Notch in cancer and development. (Source: Carcinogenesis)
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Tags: Cancer, Expression, Genes, glioma, NCR
Posted in Cancer |