Identification of Genes Mediating Chemo-Sensitivity in Human Mammary Cells

摘要

Our working hypothesis is that loss of function of a number of diverse checkpoint molecules will lead to the proliferation of chemo-resistance tumor bells. Besides the p53 pathway, relatively little is known regarding other checkpoint molecules whose loss of function results in chemo-resistance. This is probably due to the fact that loss of function of these molecules occurs through very subtle genetic alterations which are not easily detected by any current molecular techniques. Research being performed under this award is focusing on the identification of genes whose loss of function results in the proliferation of malignant epithelial cells that are resistant to the cytotoxic action of taxol, a microtubule formation inhibitor that is used in the treatment of breast cancer. This is being performed with a novel system based on a recently described technique (8) that allows for the isolation of genes encoding selectable recessive phenotypes. Identifying molecular pathways that are altered in chemo-resistance tumor cells will be critical for the future design of novel therapeutic strategies restoring chemo-sensitivity to chemo-resistant breast tumor cells.