PurposeThis study aimed to investigate the regulatory roles of estrogen receptor beta (ERβ) on gastric cancer (GC) cells, and reveal the potential mechanisms relating to nuclear factor-kappa B (NF-κB) signaling.MethodsGC cell lines SGC7901 and MKN45 were transfected with pEGFP-C1-ERβ to overexpress ERβ, and treated with PMA (a NF-κB activator) to activate NF-κB signaling. The cell proliferation and migration, as well as the formation of vessel-like structures in human venous endothelial cells (HUVECs) were detected. The expression of ERβ, NF-κB p65, p-NF-κB p65, Ki67 (a proliferation marker), vascular endothelial growth factor A (VEGF-A) and matrix metalloproteinase 2 (MMP-2), the DNA binding activity of NF-κB p65, the content of VEGF-A, and the activity of MMP-2 were detected in SGC7901 and MKN45 cells.ResultsThe transfection of pEGFP-C1-ERβ significantly increased the expression of ERβ in SGC7901 and MKN45 cells (P < 0.05). Overexpression of ERβ in SGC7901 and MKN45 cells significantly decreased the cell activity, cell number in G2/M phase, cell migration, the expression of Ki67, VEGF-A and MMP-2, VEGF-A content, MMP-2 activity, as well as the number of vessel-like structures formed by HUVECs (P < 0.05). Overexpression of ERβ also significantly decreased the DNA binding activity and the expression of p-NF-κB p65 in SGC7901 and MKN45 cells (P < 0.05). The anti-tumor effect of ERβ overexpression on GC cells was reversed by the intervention of PMA (P < 0.05).ConclusionOverexpression of ERβ inhibited the proliferation, migration, and angiogenesis of GC cells through inhibiting NF-κB signaling.
PurposeThis study aimed to explore the role of Estrogen Receptor-β (ERβ)-mediated Notch signaling pathway in the regulation of proliferation and apoptosis in liver cancer cells.MethodsHepG2 cells (Pbi-EGFP-ER) were transfected with ERβ that mediated by liposome, and normal HepG2 cells (Blank) and empty plasmid-transfected HepG2 cells (Pbi-EGFP-C) were used as controls. Then, Huh7 cells were transfected with shERβ lentivirus to knock down ERβ expression. The Huh7 cells were divided into three groups including Blank, experimental group (shERβ) and negative group (shLuc). Then, qRT-PCR, Western blot, CCK-8 assay, cell scratch assay, Transwell assay, Annexin V-FITC and PI double staining were performed based on these groups. Finally, a mouse xenograft model was constructed to verify the regulation of ERβ on Notch signaling pathway in liver cancer.ResultsIn HepG2 cells, the ERβ expression in Pbi-EGFP-E group was higher than that in Blank and Bi-EGFP-C group. Overexpression of ERβ inhibited HepG2 cell proliferation, migration, invasion and Ki67 protein expression, as well as promoted apoptosis, Bcl-2 and Bax expression. Overexpression of ERβ decreased Notch1, Notch2 and Hes1 expression. In Huh7 cells, the effect of low ERβ expression was contrary to that of high ERβ expression. The shERβ + DAPT group reversed the effect of shERβ on the volume and weight of transplanted tumors.ConclusionERβ may inhibit the development of liver cancer and promote apoptosis via inhibiting the Notch pathway.
Abstract:The E26 transformation-specific (ETS) family of transcription factors plays an important role in osteogenic differentiation. Whether GA-binding protein b2 (GABPb2), a member of the ETS family, is involved in osteogenic differentiation has not been previously reported. In the present study, directed differentiation of human osteoblast-like Saos-2 cells was induced and validated by examining alkaline phosphatase (ALP) activity, presence of mineralized nodule and other phenotypic characteristics of the cells on days 0, 3, 6 and 9, thus establishing their osteogenic potential. Real-time PCR revealed that similarly to the bone-specific transcription factor Runx2, the expression of Gabpb2 in Saos-2 cells also peaked on day 3 and was significantly reduced on days 6 and 9. Immunocytochemical staining showed that changes in the immunoreactivity of GABPb2 also exhibited a similar trend to that of Runx2. Initially, Runx2 was predominantly localized in the nuclei, while GABPb2 was relatively diffuse. Both exhibited a significant increase in immunoreactivity on day 3, with presence in both the nuclei and cytoplasm. By day 6, both showed a significant decrease in immunoreactivity and were mainly localized in the nuclei. Therefore, we surmise that GABPb2, as an ETS family member, may play a regulatory role in early osteoblastic differentiation and potentially act in synergy with Runx2.
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