TY - JOUR
T1 - Osteogenic genes related to the canonic WNT pathway are down-regulated in ameloblastoma
AU - Sathi, Gulsan A.
AU - Tsujigiwa, Hidetsugu
AU - Ito, Satoshi
AU - Siar, Chong Huat
AU - Katase, Naoki
AU - Tamamura, Ryo
AU - Harada, Hidemitsu
AU - Nagatsuka, Hitoshi
PY - 2012/12
Y1 - 2012/12
N2 - 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. Study Design: 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.
AB - 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. Study Design: 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.
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U2 - 10.1016/j.oooo.2012.08.453
DO - 10.1016/j.oooo.2012.08.453
M3 - Article
C2 - 23159115
AN - SCOPUS:84869380256
VL - 114
SP - 771
EP - 777
JO - Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
JF - Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
SN - 2212-4403
IS - 6
ER -