Identification of Novel Notch Target Genes in Breast Cancer

Notch signaling plays a key role in development, tissue homeostasis, and cancer. High expression levels of Notch signaling components are associated with aggressive disease and poor patient prognosis in breast cancer. Mesenchymal‐epithelial transition factor (MET) is a receptor tyrosine kinase with an established prognostic significance correlating with poor disease outcome in breast cancer patients as a result of high metastatic rate. We performed expression array analysis to identify candidate Notch target genes; we identified and validated MET as a target of NOTCH1 signaling in breast cancer. We found that NOTCH1 knockdown significantly reduces MET promoter activity, as well as expression levels of MET transcript and protein. The mechanism of NOTCH1 regulation of MET expression will be the focus of future work. To further identify candidate target genes of NOTCH1 signaling, we generated and validated a NOTCH1 antibody for use in chromatin immunoprecipitation experiments.MAS