title: Interferon-inducible guanylate binding protein (GBP)-2: a novel p53-regulated tumor marker in esophageal squamous cell carcinomas.
abstract: TP53 mutations are common in esophageal squamous cell carcinomas (SCC). To identify biological markers of possible relevance in esophageal SCC, we (i) searched for genes expressed in a p53-dependent manner in TE-1, an esophageal SCC cell line expressing the temperature-sensitive TP53 mutant V272M, and (ii) investigated the expression of one of those genes, the interferon-inducible Guanylate Binding Protein 2 (GBP-2), in esophageal SCC tissues. Clontech Human Cancer 1.2 arrays containing 1,176 human cancer gene-related sequences were used to identify differentially expressed genes in TE-1 cells at permissive (32 degrees C) and nonpermissive (37 degrees C) temperatures. The expression of GBP-2 and IRF-1, its main transcriptional regulator, was analyzed by immunohistochemistry in a retrospective series of 41 esophageal SCC cases with a clear transition zone from noncancer, apparently normal epithelium to invasive cancer. The expression of the GBP-2 gene is consistently increased in TE-1 at 32 degrees C in a p53-dependent manner, as confirmed by inhibition of p53 expression by RNA interference. Increase in GBP-2 is accompanied by an increase in protein levels of IRF-1, the main transcriptional regulator of GBP-2, and in the formation of complexes between p53 and IRF-1. GBP-2 expression is significantly higher in esophageal SCC than in adjacent normal epithelium (p<0.01), in which GBP-2 staining is limited to the basal layer. Our results suggest that p53 up-regulates GBP-2 by cooperating with IRF-1. The association of GBP-2 expression with proliferative squamous cells suggests that GBP-2 may represent a marker of interest in esophageal SCC.
authors.affiliation: Molecular Carcinogenesis and Biomarkers Group, International Agency for Research on Cancer, Lyon Cedex 08, France.
authors.forename: Denise P
authors.initials: DP
authors.lastname: Guimarães
authors.forename: Ivanir M
authors.initials: IM
authors.lastname: Oliveira
authors.forename: Emanuela
authors.initials: E
authors.lastname: de Moraes
authors.forename: Geisilene R
authors.initials: GR
authors.lastname: Paiva
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Souza
authors.forename: Christoph
authors.initials: C
authors.lastname: Barnas
authors.forename: Daniele B
authors.initials: DB
authors.lastname: Olmedo
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Pinto
authors.forename: Paulo A
authors.initials: PA
authors.lastname: Faria
authors.forename: Claudia Vitoria
authors.initials: CV
authors.lastname: De Moura Gallo
authors.forename: Isabele A
authors.initials: IA
authors.lastname: Small
authors.forename: Carlos G
authors.initials: CG
authors.lastname: Ferreira
authors.forename: Pierre
authors.initials: P
authors.lastname: Hainaut
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D045744:Cell Line, Tumor; D004938:Esophageal Neoplasms / Q000378:metabolism*; D005260:Female; D019204:GTP-Binding Proteins / Q000096:biosynthesis* / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*
chemical_list: D014408:Biomarkers, Tumor; D016159:Tumor Suppressor Protein p53; C534329:GBP2 protein, human; D019204:GTP-Binding Proteins