Breast Cancer Chemoprevention by Retinoids Abstract #: F-10 Vitamin A and its natural and synthetic derivatives, retinoids, are promising chemopreventive agents for patients at risk for breast cancer. Unfortunately, most retinoids evaluated so far either do not prevent the appearance of more malignant breast cancers that have lost their dependence on estrogens for growth or must be given at such high doses to prevent new tumors that they have toxic to patients. The overall objectives of the research project are to gain a better understanding of how retinoids and their receptor proteins prevent breast cancer development and based on our mechanistic studies to identify improved retinoid as breast cancer preventive agents. Our results demonstrate that one of the retinoid receptor proteins, RAR , plays a key role in mediating the growth inhibitory effect of retinoids by inhibiting activity of oncogenes cJun and cFos and by inducing breast cancer cell death. We also show that a cell survival protein called BAG-1 can modulate retinoid activities by interacting with retinoid receptor proteins. In addition, we define a novel mechanism by which levels of RAR are regulated by a protein called COUP-TF that is lost in more malignant breast cancer. These results provide a molecular basis and novel approaches to restore or enhance anti-cancer activities of retinoids in breast cancer cells. We also establish a new mechanism to induce level of RAR in estrogen-independent breast cancer cells through TR3/RXR heterodimer by a class of new retinoids called RXR-selective retinoids, which have been shown to be able to prevent the development of breast cancer and to inhibit the growth of established breast cancer in animals. Our studies show a synergistic growth inhibitory effect with combination of different classes of retinoids, providing an approach for reducing the effective dose and toxicity of retinoids. Furthermore, we discover that a protein called TR3 is required for anti-breast cancer activity of a group of new retinoids that potently induce breast cancer cell death. Our finding that TR3 exerts its effect by migrating from the nucleus to mitochondria reveals a new paradigm in breast cancer cell death and a novel mechanism by which a nuclear transcriptional factor acts in mitochondria to induce cancer cell death. This result indicates that TR3 is an important molecular target for developing more effective therapies to successfully treat breast cancer. Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.