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Breast Cancer Stem Cells in Antiestrogen Resistance
Annual rept. 1 Aug 2011-31 Jul 2012
CREIGHTON UNIV OMAHA NE
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Our research program is to study the role and underlying mechanisms of breast cancer stemprogenitor cells in antiestrogen resistance. One central subject is to understand the function of a novel estrogen receptor variant, ER-alpha 36, in antiestrogen resistance. In the past year, we have made significant progress towards accomplishment of the tasks proposed. We demonstrated that antiestrogen resistant ER-positive breast cancer cells contain high populations of stemprogenitor cells, and the stemprogenitor cells enriched from antiestrogen sensitive ER-positive breast cancer cells are refractory to and even stimulated by antiestrogens. The effects of antiestrogens on the ER-positive breast cancer stemprogenitor involve changes of both proliferation and differentiation. We also found that ER-alpha 36 plays an important role in positive regulation of both ER-positive and negative breast cancer stemprogenitor cells and contributes to the resistance of breast cancer stemprogenitor cells to antiestrogens presumably through mediating agonist activities of antiestrogens. Further study of the role and underlying mechanisms of breast cancer stemprogenitor cells in antiestrogen resistance will not only provide important information about the function of breast cancer stemprogenitor cells in development of antiestrogen resistance, but will also lay the foundation for development of novel therapeutic approaches to interfere with antiestrogen resistance.
APPROVED FOR PUBLIC RELEASE