TRANSCRIPTION FACTOR BINDING ACTIVITY IN BREAST CANCER

DESCRIPTION (provided by applicant): Aberrant gene expression, which plays a critical role in the development and progression of cancer, has often been associated with changes in transcription factor binding activities. This proposal constitutes a new approach for studying changes in transcription factor/cis site complexes associated with the development and treatment of breast cancer. The first phase involves detecting and quantifying the transcription factor binding activities functioning in cell lines of various phenotypes, +/-drug treatment, as well as in primary tumor cells. These binding activities, both known and totally novel, will then be incorporated into a higher throughput DNA array profiling method that will allow testing large numbers of cell populations for alterations in binding activities. These cells include breast cancer cell lines exhibiting different phenotypes, cells treated with a wide variety of drugs, and primary tumor cells with varying characteristics. By comparing the profiles from these cell populations, molecular fingerprints associated with characteristics such as drug resistance, ER expression, and any other phenotypes of interest can be established. In addition, the usefulness of binding activity profiling in testing drug compounds for their effects on cancer cells regarding efficacy, toxicity, mechanism of action and drug resistance will be demonstrated. PROPOSED COMMERCIAL APPLICATION: Profiling transcription factor binding activity provides a screen for characterizing new drug compounds for efficacy, mechanism of action, toxicity and drug resistance. Also useful for testing primary tumors, and for pharmacogenomics and toxicogenomics. Stand-alone assay or in conjunction with RNA expression analysis. First application in breast cancer, but applicable to all human cancers.