title: Characterization of tumor-suppressive function of SOX6 in human esophageal squamous cell carcinoma.
abstract: OBJECTIVE
  By using cDNA microarray analysis, we identified a transcriptional factor, SOX6, was frequently downregulated in esophageal squamous cell carcinoma (ESCC). The aim of this study is to investigate the role of SOX6 in human esophageal cancer development, and to examine the prevalence and clinical significance of SOX6 downregulation in ESCC.
  
  
  METHODS
  Expressions of SOX6 mRNA in 50 ESCCs and SOX6 protein in 300 ESCCs were investigated by semiquantitative RT-PCR and immunohistochemistry, respectively. The tumor-suppressive function of SOX6 was characterized by cell growth, foci formation, wound-healing and cell invasive assays, and tumor xenograft experiment. Western blot analysis was applied to detect protein expression levels.
  
  
  RESULTS
  SOX6 was frequently downregulated in primary ESCCs in both mRNA level (29/50, 58%) and protein level (149/219, 68.0%), which was significantly associated with the poor differentiation (P = 0.029), lymph node metastases (P = 0.014), advanced TNM stage (P = 0.000), and disease-specific survival (P < 0.001). Multivariate analysis indicated that the downregulation of SOX6 (P = 0.000) was a significant independent prognostic factors for ESCC. Functional studies showed that SOX6 was able to suppress both in vitro and in vivo tumorigenic ability of ESCC cells. The tumor-suppressive mechanism of SOX6 was associated with its role in G1/S cell-cycle arrest by upregulating expressions of p53 and p21(WAF1/CIP1) and downregulating expressions of cyclin D1/CDK4, cyclin A, and β-catenin.
  
  
  CONCLUSIONS
  We provided the first evidence that SOX6 is a novel tumor-suppressor gene in ESCC development and is a potential prognostic marker in ESCC.
authors.affiliation: Department of Clinical Oncology, the First affiliated hospital, Zhengzhou University, Zhengzhou, China.
authors.forename: Yan-Ru
authors.initials: YR
authors.lastname: Qin
authors.forename: Hong
authors.initials: H
authors.lastname: Tang
authors.forename: Fajun
authors.initials: F
authors.lastname: Xie
authors.forename: Haibo
authors.initials: H
authors.lastname: Liu
authors.forename: Yinghui
authors.initials: Y
authors.lastname: Zhu
authors.forename: Jiaoyu
authors.initials: J
authors.lastname: Ai
authors.forename: Leilei
authors.initials: L
authors.lastname: Chen
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Dora L
authors.initials: DL
authors.lastname: Kwong
authors.forename: Li
authors.initials: L
authors.lastname: Fu
authors.forename: Xin-Yuan
authors.initials: XY
authors.lastname: Guan
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D015536:Down-Regulation; D004938:Esophageal Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D015999:Multivariate Analysis; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055755:SOXD Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D016019:Survival Analysis; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D012333:RNA, Messenger; C486270:SOX6 protein, human; D055755:SOXD Transcription Factors; D025521:Tumor Suppressor Proteins