Identification of the Mechanisms Underlying Antiestrogen Resistance: Breast Cancer Research Partnership between FIU-UM Braman Family Breast Cancer Institute
Annual summary, 18 May 2007-17 May 2008
FLORIDA INTERNATIONAL UNIV MIAMI
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This research proposal has two primary objectives which are to 1 increase FIU investigators research expertise and competitive ability to succeed as independent breast cancer researchers and 2 to execute research with the promise of identifying molecular causes of breast tumor resistance to antiestrogen therapy. This research is of significant merit because of its clinical relevance to breast cancer. Secondly, the research accomplishments through the FIUBFBCI training program will lead to FIU investigator publications in peer-reviewed journals that will facilitate the further advancement of the FIU investigators. We proposed to investigate how reactive oxygen species ROS-induced redox signaling pathways in breast cancer cells may contribute to molecular mechanisms of antiestrogen resistance. Our hypothesis is that the conversion of breast tumors to a tamoxifen-resistant phenotype is associated with a progressive shift towards a pro-oxidant environment of cells as a result of oxidative stress. We postulate that excess ROS levels induce both CDC25A and change p27 phosphorylation promoting the loss of its inhibitory function and leading to antiestrogen resistance. We will investigate whether reducing the oxidative environment of breast cancer cells will restore the anti-proliferative action of tamoxifen and other antiestrogens by repressing CDC25A and altering p27 phosphorylation and restoring p27 function.
- Medicine and Medical Research