Use Of Insertional Mutagenesis To Discover Novel Mechanisms Of Drug Resistance In Breast Cancer

Resistance to chemotherapy remains a major barrier to the successful treatment of breast cancer. We have used a novel method, the VBIM system, that is capable of randomly modifying gene expression, which confers resistance to anti-cancer drugs that are currently being used in clinical therapies. Through inverse PCR, it is able to identify the insertion position, thus identify the modulated gene, and connect the genotype to phenotype. In the initial experiments, we discovered that down-regulation of the transcription repressor ZIP and over-expression of nuclear pore complex component NUP210 posibly confers Tamoxifen and 5-FU drug resistance, respectively. Two other genes were also identified in resistance to Tamoxifen, and their exact mechanisms are being researched.