Knockdown of ER‐α36 expression inhibits glioma proliferation, invasion and epithelial‐to‐mesenchymal transition

Abstract

Estrogen receptor-α36 (ER-α36), 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-α36 in glioma proliferation and invasion remains unknown. Here, we explored the function of ER-α36 in glioma cells, using U87 and U251 cell lines. We found that ER-α36 was upregulated in glioma tissues compared to adjacent nontumor tissues. In U87 and U251 glioma cell lines, inhibition of ER-α36 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-α36 knockdown.We also found that inhibition of ER-α36 inactivated both PI3K/AKT and MEK/ERK signals. Taken together, these data indicated that overexpression of ER-α36 is associated with glioma proliferation and progression but that inhibition of ER-α36 leads to suppressed invasion and the epithelial-tomesenchymal transition via PI3K/AKT and MEK/ERK pathway inactivation in glioma cells.