title: High α-defensin and S100A7 expression and missing DOC-1 down-regulation characterize irritation fibromas of the oral cavity and may counteract malignant transformation.
abstract: OBJECTIVE
  The purposes of this study were to analyze the gene expression pattern of antimicrobial peptides, tumor suppressors, growth factors, matrix metalloproteases, and inflammatory cytokines and chemokines in oral irritation fibromas and to identify genes with protective effects against malignant transformation in benign proliferating tumors of the oral mucosa.
  
  
  METHODS
  Biopsies of irritation fibromas (n = 15) and healthy gingiva (n = 15) were obtained during routine surgical procedures. RNA was extracted according to standard protocols, and transcription levels of CCL20, DEFA 1/3, DEFA 4, S100A7, DOC-1, interleukin (IL) 1β, IL-6, IL-8, IL-10, tumor necrosis factor α, Cox-2, matrix metalloproteinase 1 (MMP-1), MMP-2, MMP-3, MMP-8, MMP-9, transforming growth factor β1, transforming growth factor α, and keratinocyte growth factor were analyzed by real-time polymerase chain reaction. In addition, immunostaining was performed to visualize the transcription products of the genes of interest in fibroma tissue as well as in healthy gingiva.
  
  
  RESULTS
  The gene expression of S100A7 was 11.3-fold and that of DEFA 1/3 was 14-fold higher in irritation fibromas than in healthy gingiva, whereas the expression of MMP-3 and of inflammation markers IL-1β, IL-6, IL-8, tumor necrosis factor α, and Cox-2 was reduced. Profound down-regulation of DOC-1 gene expression, characteristic for proliferating malignant tumors of the oral cavity, was in irritation fibromas not verifiable.
  
  
  CONCLUSIONS
  Changes in the expression pattern of S100A7, DEFA 1/3, and MMP-3 seem to be involved in the development of irritation fibromas, whereas chronic inflammation might be of less importance. Overexpression of S100A7, but missing down-regulation of the tumor-suppressor gene DOC-1, might exert protective effects and counteract malignant transformation of benign, proliferating lesions of the oral cavity.
authors.affiliation: Department of Periodontology, University of Bonn, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Winter
authors.forename: Annette
authors.initials: A
authors.lastname: Pantelis
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Allam
authors.forename: Natalija
authors.initials: N
authors.lastname: Novak
authors.forename: Rudolf
authors.initials: R
authors.lastname: Reich
authors.forename: Markus
authors.initials: M
authors.lastname: Martini
authors.forename: Stefaan
authors.initials: S
authors.lastname: Bergé
authors.forename: James
authors.initials: J
authors.lastname: Deschner
authors.forename: Soeren
authors.initials: S
authors.lastname: Jepsen
authors.forename: Matthias
authors.initials: M
authors.lastname: Wenghoefer
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D001706:Biopsy; D002471:Cell Transformation, Neoplastic; D015536:Down-Regulation; D005350:Fibroma / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D005887:Gingival Neoplasms / Q000235:genetics*; D006801:Humans; D007124:Immunoenzyme Techniques; D019278:Matrix Metalloproteinase 3 / Q000235:genetics; D015513:Oncogene Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins / Q000235:genetics*; D023084:alpha-Defensins / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C401561:CDK2AP2 protein, human; D015513:Oncogene Proteins; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins; C089242:S100A7 protein, human; D023084:alpha-Defensins; C406413:human neutrophil peptide 1; C406427:human neutrophil peptide 3; D019278:Matrix Metalloproteinase 3