Estrogen-independent effects of ER-α36 in ER-negative breast cancer

Estrogen receptor-alpha 36 (ER-alpha 36) is a variant of ER-alpha that has been found to be expressed in conventional ER (ER-alpha 66)-negative breast cancer cell lines and human breast cancer samples. In this study, we found that, using immunohistochemical study. ER-alpha 36 expression was significantly higher in ER-negative tumors than in ER-positive tumors although the expression was not associated with other clinicopathological characteristics. We then constructed an ER-alpha 36-specific microRNA hairpin vector and established stable ER-alpha 36 knockdown cells, and found that the knockdown cells were more sensitive to paclitaxel; the c-Jun N-terminal kinase pathway appeared to be involved in the mechanism. Downregulation of ER-alpha 36 also resulted in decreased migration and invasion. These changes were estrogen independent. Our findings indicated that target ER-alpha 36 may be a strategy for treating ER-negative breast cancers. (c) 2012 Elsevier Inc. All rights reserved.