Abstract
BackgroundIt is well known that estrogen receptor α (ERα) participates in the pathogenic progress of breast cancer, hepatocellular carcinoma and head and neck squamous cell carcinoma. In neuroblastoma cells and related cancer clinical specimens, moreover, the ectopic expression of ERα has been identified. However, the detailed function of ERα in the proliferation of neuroblastoma cell is yet unclear.MethodsThe transcriptional activity of ETS-1 (E26 transformation specific sequence 1) was measured by luciferase analysis. Western blot assays and Real-time RT-PCR were used to examine the expression of ERα, ETS-1 and its targeted genes. The protein-protein interaction between ERα and ETS-1 was determined by co-IP and GST-Pull down assays. The accumulation of ETS-1 in nuclear was detected by western blot assays, and the recruitment of ETS-1 to its targeted gene’s promoter was tested by ChIP assays. Moreover, SH-SY5Y cells’ proliferation, anchor-independent growth, migration and invasion were quantified using the MTT, soft agar or Trans-well assay, respectively.ResultsThe transcriptional activity of ETS-1 was significantly increased following estrogen treatment, and this effect was related to ligand-mediated activation of ERα. The interaction between the ERα and ETS-1 was identified, and enhancement of ERα activation would up-regulate the ETS-1 transcription factor activity via modulating its cytoplasm/nucleus translocation and the recruitment of ETS-1 to its target gene’s promoter. Furthermore, treatment of estrogen increased proliferation, migration and invasion of neuroblastoma cells, whereas the antagonist of ERα reduced those effects.ConclusionsIn this study, we provided evidences that activation of ERα promoted neuroblastoma cells proliferation and up-regulated the transcriptional activity of ETS-1. By investigating the role of ERα in the ETS-1 activity regulation, we demonstrated that ERα may be a novel ETS-1 co-activator and thus a potential therapeutic target in human neuroblastoma treatment.
Highlights
It is well known that estrogen receptor α (ERα) participates in the pathogenic progress of breast cancer, hepatocellular carcinoma and head and neck squamous cell carcinoma
Estrogen enhances the transcriptional activity of E26 transformation specific sequence (ETS-1) To discover the role estrogen plays in regulating the transcriptional activity of ETS-1, a common endogenous estrogen E2 was employed in luciferase assays
SH-SY5Y cells were co-transfected with ETS-1 binding site ETS binding sequence (EBS)-Luc reporters
Summary
It is well known that estrogen receptor α (ERα) participates in the pathogenic progress of breast cancer, hepatocellular carcinoma and head and neck squamous cell carcinoma. Estrogen is recognized by estrogen receptors (ERs) [1] Among these nuclear receptors, ERα contains a ligand-independent activation function domain 1 (AF-1 domain) in N-terminal and an AF-2 domain. Cao et al BMC Cancer (2015) 15:491 detailed function of ERα in the proliferation, migration or invasion of neuroblastoma cells has not been uncovered. The transcription factor ETS-1 (E26 transformation specific sequence 1) belongs to ETS protein family [7] It contains an ETS domain (transcription activation domain) and a helix DNA-binding domain [7]. Some co-regulators participate in ETS-1 activity, such as SRC1 (steroid receptor coactivator 1), AIB-1 (amplified in breast cancer1) and NCoR [8, 9]. It is valuable to declare the interaction between ETS-1 and ERα
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