title: Fra-1 Regulates the Expression of HMGA1, Which is Associated with a Poor Prognosis in Human Esophageal Squamous Cell Carcinoma.
abstract: BACKGROUND
  The expression of Fos-related antigen 1 (Fra-1) affects tumor progression, migration, and invasion. In this study, we identified the genes regulated by Fra-1 in esophageal squamous cell carcinoma (ESCC).
  
  
  METHODS
  We constructed Fra-1 knockdown models via the transfection of small interfering RNA (siRNA) into ESCC cell lines (TE10, TE11). The expression levels of the genes in the knockdown models were analyzed using a microarray and a Biobase Upstream Analysis, while the expression levels of the candidate genes in the primary tumors of surgical specimens obtained from ESCC patients were determined using real-time polymerase chain reaction (PCR) and immunohistochemical staining. The clinicopathological features were then analyzed.
  
  
  RESULTS
  The Biobase Upstream Analysis showed the high-mobility-group protein-1 (HMGA1) to be a significant gene regulated by Fra-1. Actual binding of Fra-1 to the promotor region of HMGA1 was revealed in subsequent chromatin immunoprecipitation PCR experiments. Patients with a positive HMGA1 expression had a poor prognosis, and a multivariate analysis demonstrated a positive HMGA1 expression to be a significant independent prognostic factor.
  
  
  CONCLUSIONS
  HMGA1 is regulated by Fra-1 in ESCC, and the HMGA1 expression is significantly associated with a poor prognosis in ESCC patients. Downregulation of the HMGA1 expression may become a practical treatment strategy against ESCC in the future.
authors.affiliation: Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Toyozumi
authors.affiliation: Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan. i_hosino@chiba-u.jp.
authors.forename: Isamu
authors.initials: I
authors.lastname: Hoshino
authors.affiliation: Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Takahashi
authors.affiliation: Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Usui
authors.affiliation: Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Akutsu
authors.affiliation: Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Hanari
authors.affiliation: Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Murakami
authors.affiliation: Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kano
authors.affiliation: Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Akanuma
authors.affiliation: Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Suitoh
authors.affiliation: Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Matsumoto
authors.affiliation: Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Nobuhumi
authors.initials: N
authors.lastname: Sekino
authors.affiliation: Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Aki
authors.initials: A
authors.lastname: Komatsu
authors.affiliation: Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Hisahiro
authors.initials: H
authors.lastname: Matsubara
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000556:secondary* / Q000601:surgery; D002465:Cell Movement; D049109:Cell Proliferation; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D015972:Gene Expression Regulation, Neoplastic; D025741:HMGA1a Protein / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008207:Lymphatic Metastasis; D009361:Neoplasm Invasiveness; D011379:Prognosis; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D000099169:Fos-Related Antigen 1
chemical_list: D014408:Biomarkers, Tumor; D025741:HMGA1a Protein; D016760:Proto-Oncogene Proteins c-fos; D000099169:Fos-Related Antigen 1
keywords: Esophageal Squamous Cell Carcinoma; Esophageal Squamous Cell Carcinoma Cell Line; Esophageal Squamous Cell Carcinoma Patient; Significant Independent Prognostic Factor; TE11 Cell