title: Osteogenic genes related to the canonic WNT pathway are down-regulated in ameloblastoma.
abstract: OBJECTIVE
  The aim of this study was to determine the expression of essential osteogenic genes related to the canonic WNT pathway, i.e., WDR5, sFRP-2, and their downstream genes, in ameloblastoma and to clarify their biologic impact on this neoplasm.
  
  
  METHODS
  Forty-six paraffin-embedded ameloblastoma samples and ameloblastic (AM-1) and preosteoblastic (KUSA/A1) cell lines were used. Immunohistochemistry, Western blot, reverse-transcription polymerase chain reaction, and alkaline phosphatase (ALP) activity assay were performed.
  
  
  RESULTS
  WDR5, essential for osteoblast differentiation and canonic WNT pathway activation, was negative in most ameloblastoma cases and weakly expressed in AM-1 cells. Conversely, sFRP-2s was overexpressed. RUNX2 and C-MYC, downstream inductions of canonic WNT pathway activation, demonstrated weak mRNA expressions in ameloblastoma, suggesting WNT pathway impairment and WDR5 functional inactivity. Recombinant WDR5 weakly induced ALP activity of KUSA/A1 cells cultured in AM-1 conditioned medium.
  
  
  CONCLUSIONS
  These findings suggest that WNT-related bone-forming genes are down-regulated in ameloblastoma. Concurrent sFRP-2 overexpression suggests that both bone-forming and bone-inhibiting genes equally contributed to reduced bone formation in this neoplasm.
authors.affiliation: Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
authors.forename: Gulsan A
authors.initials: GA
authors.lastname: Sathi
authors.forename: Hidetsugu
authors.initials: H
authors.lastname: Tsujigiwa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ito
authors.forename: Chong Huat
authors.initials: CH
authors.lastname: Siar
authors.forename: Naoki
authors.initials: N
authors.lastname: Katase
authors.forename: Ryo
authors.initials: R
authors.lastname: Tamamura
authors.forename: Hidemitsu
authors.initials: H
authors.lastname: Harada
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Nagatsuka
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000564:Ameloblastoma / Q000235:genetics*; D001483:Base Sequence; D015153:Blotting, Western; D017931:DNA Primers; D015536:Down-Regulation; D006801:Humans; D007150:Immunohistochemistry; D007573:Jaw Neoplasms / Q000235:genetics*; D010012:Osteogenesis / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051153:Wnt Proteins / Q000235:genetics*
chemical_list: D017931:DNA Primers; D051153:Wnt Proteins; D000469:Alkaline Phosphatase