title: Involvement of epithelial cell transforming sequence-2 oncoantigen in lung and esophageal cancer progression.
abstract: OBJECTIVE
  This study aims to isolate potential molecular targets for diagnosis, treatment, and/or prevention of lung and esophageal carcinomas.
  
  
  METHODS
  We screened for genes that were frequently overexpressed in the tumors through gene expression profile analyses of 101 lung cancers and 19 esophageal squamous cell carcinomas (ESCC) by cDNA microarray consisting of 27,648 genes or expressed sequence tags. In this process, we identified epithelial cell transforming sequence 2 (ECT2) as a candidate. Tumor tissue microarray was applied to examine the expression of ECT2 protein in 242 archived non-small-cell lung cancers (NSCLC) and 240 ESCC specimens and to investigate its prognostic value. A role of ECT2 in lung and esophageal cancer cell growth and/or survival was examined by small interfering RNA experiments. Cellular invasive activity of ECT2 in mammalian cells was examined using Matrigel assays.
  
  
  RESULTS
  Northern blot and immunohistochemical analyses detected expression of ECT2 only in testis among 23 normal tissues. Immunohistochemical staining showed that a high level of ECT2 expression was associated with poor prognosis for patients with NSCLC (P = 0.0004) as well as ESCC (P = 0.0088). Multivariate analysis indicated it to be an independent prognostic factor for NSCLC (P = 0.0005). Knockdown of ECT2 expression by small interfering RNAs effectively suppressed lung and esophageal cancer cell growth. In addition, induction of exogenous expression of ECT2 in mammalian cells promoted cellular invasive activity.
  
  
  CONCLUSIONS
  ECT2 cancer-testis antigen is likely to be a prognostic biomarker in clinic and a potential therapeutic target for the development of anticancer drugs and cancer vaccines for lung and esophageal cancers.
authors.affiliation: Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan.
authors.forename: Daizaburo
authors.initials: D
authors.lastname: Hirata
authors.forename: Takumi
authors.initials: T
authors.lastname: Yamabuki
authors.forename: Daiki
authors.initials: D
authors.lastname: Miki
authors.forename: Tomoo
authors.initials: T
authors.lastname: Ito
authors.forename: Eiju
authors.initials: E
authors.lastname: Tsuchiya
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fujita
authors.forename: Masao
authors.initials: M
authors.lastname: Hosokawa
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Chayama
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Yataro
authors.initials: Y
authors.lastname: Daigo
mesh_terms: D000368:Aged; D001483:Base Sequence; D015415:Biomarkers / Q000032:analysis*; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000473:pathology; D045744:Cell Line, Tumor; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000175:diagnosis* / Q000473:pathology; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000473:pathology; D008297:Male; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000032:analysis*
chemical_list: D015415:Biomarkers; C489850:ECT2 protein, human; D011518:Proto-Oncogene Proteins