关键词：乳腺癌；雌激素类；干细胞；阻值
摘 要：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- 36, in antiestrogen resistance. In the past year, we have accomplished most of the tasks proposed. We demonstrated that antiestrogen treatment enriched breast cancer stem/progenitor cells and antiestrogens positively regulated the selfrenewal of breast cancer stem/progenitor cells. ER-negative breast cancer cells with knocked-down levels of ER- 36 have less cancer stem/progenitor cells and are sensitive to antiestrogens. We found that ER- 36 mediates agonist activities of antiestrogens such as activation of the PI3K/AKT signaling pathway. In addition, we discovered a novel anticancer agent Broussoflavonol that is able to down-regulate ER- 36 expression, induce differentiation of ER- negative breast cancer stem cells and inhibit growth of these cells. Our results thus demonstrated that ER- 36 plays an important role in the resistance of breast cancer stem/progenitor cells to antiestrogens and provided a rational to development of novel therapeutic approaches by targeting ER- 36, which will ultimately revolutionize current therapeutic approaches.