| Glioma is one of the most common brain tumors,accounting for 60%of all primary nervous system tumors.There is a significant gender difference in the incidence of glioma,the male incidence rate is 1.85 times compared to that of female.Because of the high recurrence rate,most patients died within one year after it confirmed.At present,the treatment methods of glioma include surgical resection,radiotherapy and chemotherapy.More and more research groups are studying on the targeted drugs,and trying to find the target for glioma treatment.Considering the difference in the incidence of glioma between men and women,we speculated that the treatment of glioma should start from gender-ralated receptors.ER-a36 is a novel estrogen receptor.And it is localized on the cell membrane,whose molecular mass is 35.7 kD.ER-?36 mediates membrane-initiated estrogen signaling pathways.Research on the role of ER-?36 in a variety of cancers is hot,especially its role in the development of breast cancer.But its role in glioma is not clear till now.In this study,we found that the expression of ER-?36 in tumor tissue was significantly higher than that in paracancer tissues.And when the expression of ER-?36 in glioma cell line was downregulated,the proliferation,migration and invasion of glioma cells were weakened with it.The results of xenografts tumor establishment showed that the tumorigenic ability of glioma cells was significantly decreased after ER-?36 was knocked down.Therefore,we speculate that ER-?36 may be associated with the occurrence and development of glioma,which may become a new target for glioma treatment.BackgroundGlioma is the most prevalent primary brain tumor.There is a significant gender difference in the incidence of glioma.ER-?36 is a new type of estrogen receptors,and its biological effects are attracting more and more attention.Because of the significant gender difference in the incidence of glioma,we speculated that hormone receptors may play a specific role in the development and progression of glioma.It has been reported that ER-a36-mediated rapid estrogen signaling regulates the function of breast cancer stem/progenitor cells,and ER-?36 is a key factor in the risk of breast cancer.Overexpression of ER-?36 can attenuate the efficacy and effects of chemotherapeutic drugs on breast cancer cells.More and more evidence showed that ER-?36 plays an important role in breast cancer,however,its role in the development of glioma has not been reported.ObjectsTo knock down ER-?36 in glioma cell lines,and test the proliferation,migration and invasion by MTT assay,wound healing migration assay and invasion assay.Then to find out the effect of ER-?36 on cell proliferation,migration,invasion by xenografts tumor establishment.To study the signal pathway of cell apoptosis,migration and invasion after knocking down ER-a36.MethodsThe glioma and adjacent tissues were collected,and the expression of ER-?36 in tumor tissues and paracancer tissues were detected.Using ER-?36 agonist G1 or inhibitor IC162,the changes of glioma cell's proliferation was observed,respectively.The shRNA-?36 plasmid was transfected into U87 and U251 glioma cells to construct U87 shER-?36 and U251 shER-?36 cell line,respectively.The changes of migration and invasion of glioma cells in ER-?36-knockdown cells were observed by wound healing migration assay and invasion assay.At the same time,western blot was used to detect epithelium and mesenchymal cell protein marker.We also detected the signaling pathways that may be involved in the proliferation,metastasis,and invasion of glioma.Results1)Western blot results showed that the expression of ER-a36 in tumor tissue was higher than that in paracancer tissues in 10 of 12 pair glioma samples.2)MTT results showed that the proliferation of glioma cells increased with the dose of ER-a36 specific agonist G1.ER-a36 specific inhibitor IC162 can significantly reduce the proliferation of gliomas cells.3)MTT assay confirmed that when ER-a36 was knocked down in glioma cells,the proliferation of cells was inhibited.The results of tumor growth in nude mice showed that the tumorigenic ability of glioma cells was significantly lower than that of the control group.4)The results of wound healing migration assay and invasion assay showed that ER-a3 6-knockdown can reduce the migration and invasion of glioma cells.Western blot was used to detect the epithelial and mesenchymal protein marker.The results of Western blot showed that ER-a3 6-knockdown could inhibit the EMT process of glioma cells.5)Western blot results showed that when ER-a36 was knocked down,MAPK/ERK and PI3K/AKT signaling pathway were suppressed with it.ConclusionER-a36 plays an important role in the proliferation,migration,invasion and the EMT process in glioma cells.These effects may be achieved by modulating MAPK/ERK and PI3K/AKT signaling pathway. |
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