Immediate-Early Response Genes as Targets for Breast Cancer Treatment

摘要

Immediate-early response genes play a role in both survival and death. This concept award proposed that the opposing biological activities of the immediate-early response genes were regulated by their subcellular localization. That is, the mitogenic activities of these genes occur in the nucleus through their target gene regulation, whereas their apoptosis-inducing effect occurs in the cytoplasm through their modulation of mitochondrial activities. We have studied the subcellular localization of immediate-early response genes TR3 and c-myc in response to apoptotic stimuli in breast cancer cells by confocal microscopy analysis. Our results demonstrated that TR3 migrated from the nucleus to mitochondria in response to apoptotic stimuli in breast cancer cells, while c-myc localized exclusively in the nucleus under the same treatments. Our results, therefore, suggest that inducing TR3 mitochondrial localization may be an attractive approach to induce breast cancer cell apoptosis. Thus, orphan receptor TR3 may be used as a molecular target for developing agents that induce breast cancer cell apoptosis.