Breast Cancer Stem Cells in Antiestrogen Resistance
Final rept. 1 Aug 2011-31 Jul 2014
CREIGHTON UNIV OMAHA NE
Pagination or Media Count:
Our research program is to understand the function and underlying mechanisms of a novel estrogen receptor variant, ER-alpha- 36, in antiestrogen resistance of breast cancer stemprogenitor cells. In the whole funding period, we have demonstrated 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. Finally, we discovered novel regulatory loops of ER-alpha- 36 and EGFRHER2 that play an important role in antiestrogen resistance and disruption of these loops sensitizes breast cancer stemprogenitor cells to antiestrogen. Thus, our study of the role and underlying mechanisms of breast cancer stemprogenitor cells in antiestrogen resistance not only provided important information about the function of breast cancer stemprogenitor cells in development of antiestrogen resistance, but also laid the foundation for development of novel therapeutic approaches to overcome antiestrogen resistance.
- Anatomy and Physiology
- Medicine and Medical Research