Breast Cancer Stem Cells in Antiestrogen Resistance
Abstract
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 stem/progenitor cells. In the whole funding period, we have demonstrated the stem/progenitor 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 stem/progenitor 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 stem/progenitor cells and contributes to the resistance of breast cancer stem/progenitor cells to antiestrogens presumably through mediating agonist activities of antiestrogens. Finally, we discovered novel regulatory loops of ER-alpha- 36 and EGFR/HER2 that play an important role in antiestrogen resistance and disruption of these loops sensitizes breast cancer stem/progenitor cells to antiestrogen. Thus, our study of the role and underlying mechanisms of breast cancer stem/progenitor cells in antiestrogen resistance not only provided important information about the function of breast cancer stem/progenitor cells in development of antiestrogen resistance, but also laid the foundation for development of novel therapeutic approaches to overcome antiestrogen resistance.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2014
- Accession Number
- ADA621083
Entities
People
- Guanguan Li
- Hao Deng
- Molin Wang
- Zhaoyi Wang
Organizations
- Creighton University