Knockdown of ER-alpha 36 expression inhibits glioma proliferation, invasion and epithelial-to-mesenchymal transition

Estrogen receptor-alpha 36 (ER-alpha 36), a subtype of the estrogen receptor, is reported to play roles in tumorigenesis and tamoxifen resistance in several tumors, especially breast cancer. However, the role of ER-alpha 36 in glioma proliferation and invasion remains unknown. Here, we explored the function of ER-alpha 36 in glioma cells, using U87 and U251 cell lines. We found that ER-alpha 36 was upregulated in glioma tissues compared to adjacent nontumor tissues. In U87 and U251 glioma cell lines, inhibition of ER-alpha 36 expression by shRNA suppressed cell proliferation and invasion. In addition, the expression of an epithelial marker, ZO-1, was upregulated while that of one mesenchymal marker, N-cadherin, was downregulated with ER-alpha 36 knockdown. We also found that inhibition of ER-alpha 36 inactivated both PI3K/AKT and MEK/ERK signals. Taken together, these data indicated that overexpression of ER-alpha 36 is associated with glioma proliferation and progression but that inhibition of ER-alpha 36 leads to suppressed invasion and the epithelial-to-mesenchymal transition via PI3K/AKT and MEK/ERK pathway inactivation in glioma cells.