ER-α36 mediates estrogen-stimulated MAPK/ERK activation and regulates migration, invasion, proliferation in cervical cancer cells

作者：Sun, Qing; Liang, Ying; Zhang, Tianli; Wang, Kun; Yang, Xingsheng^*

来源：Biochemical and Biophysical Research Communications, 2017, 487(3): 625-632.

DOI：10.1016/j.bbrc.2017.04.105

• Cervical cancer
• ER-alpha 36
• MAPK/ERK
• Migration
• Invasion
• Proliferation

Objective: Estrogen receptor alpha 36 (ER-alpha 36), a truncated variant of ER-alpha, is different from other nuclear receptors of the ER-alpha family. Previous findings indicate that ER-alpha 36 might be involved in cell growth, proliferation, and differentiation in carcinomas and primarily mediates non-genomic estrogen signaling. However, studies on ER-alpha 36 and cervical cancer are rare. This study aimed to detect the expression of ER-alpha 36 in cervical cancer; the role of ER-alpha 36 in 17-beta-estradiol (E2)-induced invasion, migration and proliferation of cervical cancer; and their probable molecular mechanisms. @@@ Methods: Immunohistochemistry and immunofluorescence were used to determine the location of ER-alpha 36 in cervical cancer tissues and cervical cell lines. CaSki and HeLa cell lines were transfected with lentiviruses to establish stable cell lines with knockdown and overexpression of ER-alpha 36. Wound healing assay, transwell invasion assay, and EdU incorporation proliferation assay were performed to evaluate the migration, invasion, and proliferation ability. The phosphorylation levels of mitogen-activated protein kinases/extracellular signal-regulated kinase (MAPK/ERK) signaling molecules were examined with western blot analysis. @@@ Results: ER-alpha 36 expression was detected in both cervical cell lines and cervical cancer tissues. Down regulation of ER-alpha 36 significantly inhibited cell invasion, migration, and proliferation. Moreover, upregulation of ER-alpha 36 increased the invasion, migration, and proliferation ability of CaSki and HeLa cell lines. ER-alpha 36 mediates estrogen-stimulated MAPK/ERK activation. @@@ Conclusion: ER-alpha 36 is localized on the plasma membrane and cytoplasm in both cervical cancer tissues and cell lines. ER-alpha 36 mediates estrogen-stimulated MAPK/ERK activation and regulates migration, invasion, proliferation in cervical cancer cells.

• 出版日期2017-6-3
• 单位山东大学