Breast Cancer Stem Cells in Antiestrogen Resistance

Abstract

Abstract : Our research program is to study the role and underlying mechanisms of breast cancer stem/progenitor 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 stem/progenitor cells, and 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. Further study of the role and underlying mechanisms of breast cancer stem/progenitor cells in antiestrogen resistance will not only provide important information about the function of breast cancer stem/progenitor cells in development of antiestrogen resistance, but will also lay the foundation for development of novel therapeutic approaches to interfere with antiestrogen resistance.