title: Benzo (a) pyrene induced tumorigenesity of human immortalized oral epithelial cells: transcription profiling.
abstract: BACKGROUND
  The present study was designed to examine and analyze the global gene expression changes during the tumorigenesis of a human immortalized oral epithelial cell line, and search for the possible genes that may play a role in the carcinogenesis of oral cancer associated with benzo (a) pyrene.
  
  
  METHODS
  The human immortalized oral epithelial cells, which have been established through transfection of E6/E7 genes of human papillomavirus type 16 and proved to be non-tumorigenic in nude mice, were treated with benzo (a) pyrene. Tumorigenicity of the treated cells were examined through nude mice subcutaneous injection. The global gene expression profiles of immortalized cells and the tumorigenic cells were acquired through hybridization of a microarray of Affymetrix U133 plus 2.0. The data were analyzed using Spring 7.0 software and treated statistically using one-way analysis of variance (ANOVA). The differentially expressed genes were classified using a Venn diagram and annotated with gene ontology. Several highlighted genes were validated in cells using a real-time polymerase chain reaction.
  
  
  RESULTS
  There were 883 differentially expressed genes during the tumorigenesis and most of them changed expression in the early stage of tumorigenesis. These genes mainly involved in macromolecule metabolism and signal transduction, possessed the molecular function of transition metal ion binding, nucleotide binding and kinase activity; their protein products were mainly integral to membranes or localized in the nucleus and cytoskeleton. The expression patterns of IGFBP3, S100A8, MAP2K, KRT6B, GDF15, MET were validated in cells using a real-time polymerase chain reaction; the expression of IGFBP3 was further validated in clinical oral cancer specimens.
  
  
  CONCLUSIONS
  This study provides the global transcription profiling associated with the tumorigenesis of oral epithelial cells exposed to benzo (a) pyrene; IGFBP3 may play a potential role in the initiation of oral cancer related to benzo (a) pyrene exposure.
authors.affiliation: Department of Oral and Maxillofacial Surgery, College of Stomatology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Jin-zhong
authors.initials: JZ
authors.lastname: Li
authors.forename: Hong-ya
authors.initials: HY
authors.lastname: Pan
authors.forename: Jia-wei
authors.initials: JW
authors.lastname: Zheng
authors.forename: Xiao-jian
authors.initials: XJ
authors.lastname: Zhou
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.forename: Wan-tao
authors.initials: WT
authors.lastname: Chen
authors.forename: Zhi-yuan
authors.initials: ZY
authors.lastname: Zhang
mesh_terms: D001564:Benzo(a)pyrene / Q000633:toxicity*; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D018031:Connexin 43 / Q000235:genetics; D020869:Gene Expression Profiling; D055436:Growth Differentiation Factor 15 / Q000235:genetics; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins / Q000235:genetics; D009062:Mouth Neoplasms / Q000139:chemically induced* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D018031:Connexin 43; C526140:GDF15 protein, human; C500216:GJA1 protein, human; D055436:Growth Differentiation Factor 15; C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins; D001564:Benzo(a)pyrene