title: Expression of tumor necrosis factor alpha, TNF-related apoptosis-inducing ligand, and their associated molecules in ameloblastomas.
abstract: BACKGROUND
  To clarify the roles of the apoptosis signaling pathway mediated by death receptors in oncogenesis and cytodifferentiation of odontogenic tumors, expression of tumor necrosis factor alpha (TNFalpha), TNF-related apoptosis-inducing ligand (TRAIL), and their associated molecules was analyzed in ameloblastomas as well as in tooth germs.
  
  
  METHODS
  Tissue specimens of 10 tooth germs, 40 benign ameloblastomas, and five malignant ameloblastomas were examined by reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry to determine the expression of TNFalpha, TNF receptor I (TNFRI), TRAIL, TRAIL receptor 1 (TRAIL-R1), TRAIL-R2, caspase-8, and nuclear factor-kappaB (NF-kappaB).
  
  
  RESULTS
  Expression of TNFalpha, TNFRI, TRAIL, TRAIL-R1, TRAIL-R2, and NF-kappaB mRNA was detected in most samples of normal and neoplastic odontogenic tissues. Expression of caspase-8 mRNA was identified in six of 33 ameloblastomas, but not in 10 tooth germs or one malignant ameloblastoma. Immunohistochemical reactivity for TNFalpha, TRAIL, their receptors, and NF-kappaB was detected in both normal and neoplastic odontogenic tissues. Epithelial expression of TNFalpha was focal in about 50% of tooth germs and ameloblastomas, and TNFalpha expression in neoplastic cells was significantly higher in follicular ameloblastomas than in plexiform ameloblastomas. TRAIL reactivity was evident in epithelial cells neighboring the basement membrane. Receptors for TNFalpha and TRAIL were diffusely expressed in both normal and neoplastic odontogenic epithelium. Expression of caspase-8 was found in some neoplastic cells in three of 37 ameloblastomas, but not in 10 tooth germs or five malignant ameloblastomas. Nuclear NF-kappaB expression was much lower than cytoplasmic expression in both normal and neoplastic odontogenic epithelium.
  
  
  CONCLUSIONS
  Expression of TNFalpha, TRAIL, and their receptors in tooth germs and ameloblastomas suggests that these death factors might be involved in cytodifferentiation of odontogenic epithelium and tissue structuring of ameloblastomas. Expression of caspase-8 and NF-kappaB suggests that signaling of TNFalpha and TRAIL minimally affects the biological properties of odontogenic epithelial components.
authors.affiliation: Division of Oral Pathology, Department of Oral Medicine and Surgery, Tohoku University Graduate School of Dentistry, Sendai 980-8575, Japan. kumamoto@mail.tains.tohoku.ac.jp
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kumamoto
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Ooya
mesh_terms: D000564:Ameloblastoma / Q000378:metabolism*; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D053181:Caspase 8; D020169:Caspases / Q000096:biosynthesis; D006801:Humans; D007124:Immunoenzyme Techniques; D007573:Jaw Neoplasms / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D016328:NF-kappa B / Q000096:biosynthesis; D012333:RNA, Messenger / Q000032:analysis; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D018709:Statistics, Nonparametric; D053221:TNF-Related Apoptosis-Inducing Ligand; D014083:Tooth Germ / Q000378:metabolism; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D051017:Apoptosis Regulatory Proteins; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D012333:RNA, Messenger; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; D053221:TNF-Related Apoptosis-Inducing Ligand; C105190:TNFRSF10A protein, human; C505639:TNFRSF10B protein, human; C505653:TNFSF10 protein, human; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins; D014409:Tumor Necrosis Factor-alpha; C505530:CASP8 protein, human; D053181:Caspase 8; D020169:Caspases