Mitosis-Specific Negative Regulation of EGF-Receptor in Breast Cancer: Molecular Mechanisms, Biological Significance and Therapeutic Application

摘要

The purpose of this project is to study the regulation of EGFR during M-phase. Normally EGFR is negatively regulated during M-phase, however when EGFR is overexpressed it is found to bypass this regulation. We plan to use this negative regulation of EGFR to develop a therapeutic strategy that uses the combination of EGF-PE and taxol as treatment for patients. In trying to understand the mechanism of action of EGFR we have found specific phosphorylation spots of EGFR in M-phase. We have also shown that using the chimeric toxin EGF-PE and taxol together we can specifically target cells which overexpress EGFR, and protect normal cells, a concept that if proven in vivo can benefit patients in the future. In addition to the proposed work we have also found that cyclin D1 can be upregulated by beta-catenin and that beta-catenin can serve as a poor prognostic factor in patients. Furthermore, in trying to further understand beta-catenin signaling we have found that beta-catenin can interact with and inhibits NF-kappa B. These studies can provide useful information so we can better understand the signaling involved in breast cancer, and hopefully we can use this to find better treatments for patients.