title: Estrogen receptor α enhances the transcriptional activity of ETS-1 and promotes the proliferation, migration and invasion of neuroblastoma cell in a ligand dependent manner.
abstract: BACKGROUND
  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. 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.
  
  
  METHODS
  The 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.
  
  
  RESULTS
  The 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.
  
  
  CONCLUSIONS
  In 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.
authors.affiliation: Department of Neurosurgery, Institute of Neurology, General Hospital of Shenyang Military Area Command, Shenyang Northern Hospital, 83 Wenhua Road, Shenhe District, Shenyang City, Liaoning Province, 110016, PR China. atocaopeng@hotmail.com.
authors.forename: Peng
authors.initials: P
authors.lastname: Cao
authors.affiliation: Department of Pharmacy, General Hospital of Shenyang Military Area Command, Shenyang Northern Hospital, 83 Wenhua Road, Shenhe District, Shenyang City, Liaoning Province, 110016, PR China. fengfanbio@126.com.
authors.forename: Fan
authors.initials: F
authors.lastname: Feng
authors.affiliation: Institute of Radiation Medicine, Military Medical Science Academy of the Chinese PLA, 27 Taiping Road, Beijing City, 100850, PR China. dongguofu052@126.com.
authors.forename: Guofu
authors.initials: G
authors.lastname: Dong
authors.affiliation: Department of Neurosurgery, Institute of Neurology, General Hospital of Shenyang Military Area Command, Shenyang Northern Hospital, 83 Wenhua Road, Shenhe District, Shenyang City, Liaoning Province, 110016, PR China. chunyongyuljzy@126.com.
authors.forename: Chunyong
authors.initials: C
authors.lastname: Yu
authors.affiliation: Department of Neurosurgery, Institute of Neurology, General Hospital of Shenyang Military Area Command, Shenyang Northern Hospital, 83 Wenhua Road, Shenhe District, Shenyang City, Liaoning Province, 110016, PR China. szfengljzy@126.com.
authors.forename: Sizhe
authors.initials: S
authors.lastname: Feng
authors.affiliation: Department of Urology, General Hospital of the Chinese PLA, 28 Fuxing Road, Beijing City, 100853, PR China. 18911026232@126.com.|Key Laboratory of Cardiovascular Medicine Research, Ministry of Education, Harbin Medical University, Harbin, 150081, PR China. 18911026232@126.com.
authors.forename: Erlin
authors.initials: E
authors.lastname: Song
authors.affiliation: Department of Pharmacy, General Hospital of Shenyang Military Area Command, Shenyang Northern Hospital, 83 Wenhua Road, Shenhe District, Shenyang City, Liaoning Province, 110016, PR China. guobingsh@126.com.
authors.forename: Guobing
authors.initials: G
authors.lastname: Shi
authors.affiliation: Department of Neurosurgery, Institute of Neurology, General Hospital of Shenyang Military Area Command, Shenyang Northern Hospital, 83 Wenhua Road, Shenhe District, Shenyang City, Liaoning Province, 110016, PR China. yongliang2003@163.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Department of Neurosurgery, Institute of Neurology, General Hospital of Shenyang Military Area Command, Shenyang Northern Hospital, 83 Wenhua Road, Shenhe District, Shenyang City, Liaoning Province, 110016, PR China. guobiaol_glioma@126.com.
authors.forename: Guobiao
authors.initials: G
authors.lastname: Liang
mesh_terms: D063646:Carcinogenesis; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D047628:Estrogen Receptor alpha / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008024:Ligands; D009361:Neoplasm Invasiveness / Q000235:genetics; D009447:Neuroblastoma / Q000235:genetics* / Q000473:pathology; D060066:Protein Interaction Maps / Q000235:genetics; D050784:Proto-Oncogene Protein c-ets-1 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation / Q000235:genetics*
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D008024:Ligands; D050784:Proto-Oncogene Protein c-ets-1