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Novel Role Of Erbb-2 In Inhibition Of Jagged-1-Mediated Trans-Activation Of Notch In Breast Cancer, Kinnari Pandya
Novel Role Of Erbb-2 In Inhibition Of Jagged-1-Mediated Trans-Activation Of Notch In Breast Cancer, Kinnari Pandya
Dissertations
The ErbB-2 gene is amplified and the resulting protein product overexpressed in 15-30% of breast tumors, and associated with aggressive behavior and poor overall survival. Currently, there are two FDA approved therapies targeting ErbB-2 for the treatment of ErbB-2 positive breast cancer: trastuzumab, a humanized monoclonal antibody is directed against the extracellular domain of ErbB-2 and lapatinib, a dual EGFR/ErbB-2 tyrosine kinase inhibitor. Unfortunately, anti-ErbB-2 therapy resistance remains a major problem in metastatic breast cancer. Our data suggested that gene amplification or overexpression of ErbB-2 inhibits Notch-1 transcriptional activity and trastuzumab or lapatinib increased
Notch-1 transcriptional activity. Furthermore, Notch-1 is …