Influence of the Tumor Microenvironment on Genomic Changes Conferring Chemoresistance in Breast Cancer.

摘要

Chemoresistance is a major hurdle against to successful breast cancer therapy. Although hypoxic tumor microenvironment has been associated with chemoresistance, molecular mechanisms driven by the tumor hypoxia remain not fully understood. The aim in this proposal is to elucidate the mechanism by which the hypoxic tumor microenvironment influences chemoresistance throughout in vivo monitoring and comprehensive profiling of cancer cells originated from the tumor hypoxia. During the first fiscal year, I have developed a method to trace tumor cells that were exposed to hypoxia by recruitment of hypoxia-responsible Cre (5xHRE-CREM) and multi-fluorescent gene (Brainbow) plasmids. In addition, I generated multiple fluorescent labeling technique and a transgenic mouse that would be useful to examine heterogeneous primary tumor cells in a single cell resolution. All of findings and developed methods would be useful to examine individual tumor cell behavior in vivo and for molecular profiling of cell population that originated from a specific pathologic condition, like as tumor hypoxia.