Sun Qing, Liang Ying, Zhang Tianli, Wang Kun, Yang Xingsheng
Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, Shandong, China.
Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, Shandong, China.
Biochem Biophys Res Commun. 2017 Jun 3;487(3):625-632. doi: 10.1016/j.bbrc.2017.04.105. Epub 2017 Apr 20.
Estrogen receptor alpha 36 (ER-α36), a truncated variant of ER-α, is different from other nuclear receptors of the ER-α family. Previous findings indicate that ER-α36 might be involved in cell growth, proliferation, and differentiation in carcinomas and primarily mediates non-genomic estrogen signaling. However, studies on ER-α36 and cervical cancer are rare. This study aimed to detect the expression of ER-α36 in cervical cancer; the role of ER-α36 in 17-β-estradiol (E2)-induced invasion, migration and proliferation of cervical cancer; and their probable molecular mechanisms.
Immunohistochemistry and immunofluorescence were used to determine the location of ER-α36 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-α36. 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.
ER-α36 expression was detected in both cervical cell lines and cervical cancer tissues. Downregulation of ER-α36 significantly inhibited cell invasion, migration, and proliferation. Moreover, upregulation of ER-α36 increased the invasion, migration, and proliferation ability of CaSki and HeLa cell lines. ER-α36 mediates estrogen-stimulated MAPK/ERK activation.
ER-α36 is localized on the plasma membrane and cytoplasm in both cervical cancer tissues and cell lines. ER-α36 mediates estrogen-stimulated MAPK/ERK activation and regulates migration, invasion, proliferation in cervical cancer cells.
雌激素受体α36（ER-α36）是ER-α的一种截短变体，与ER-α家族的其他核受体不同。先前的研究结果表明，ER-α36可能参与癌症中的细胞生长、增殖和分化，并且主要介导非基因组雌激素信号传导。然而，关于ER-α36与宫颈癌的研究很少。本研究旨在检测ER-α36在宫颈癌中的表达；ER-α36在17-β-雌二醇（E2）诱导的宫颈癌侵袭、迁移和增殖中的作用；以及它们可能的分子机制。
采用免疫组织化学和免疫荧光法确定ER-α36在宫颈癌组织和宫颈细胞系中的定位。用慢病毒转染CaSki和HeLa细胞系，建立ER-α36敲低和过表达的稳定细胞系。进行伤口愈合试验、Transwell侵袭试验和EdU掺入增殖试验，以评估迁移、侵袭和增殖能力。用蛋白质印迹分析检测丝裂原活化蛋白激酶/细胞外信号调节激酶（MAPK/ERK）信号分子的磷酸化水平。
在宫颈细胞系和宫颈癌组织中均检测到ER-α36表达。ER-α36的下调显著抑制细胞侵袭、迁移和增殖。此外，ER-α36的上调增加了CaSki和HeLa细胞系的侵袭、迁移和增殖能力。ER-α36介导雌激素刺激的MAPK/ERK激活。
ER-α36定位于宫颈癌组织和细胞系的质膜和细胞质中。ER-α36介导雌激素刺激的MAPK/ERK激活，并调节宫颈癌细胞的迁移、侵袭和增殖。
