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.

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.

• Authors: Gulsan A Sathi, Hidetsugu Tsujigiwa, Satoshi Ito, Chong Huat Siar, Naoki Katase, Ryo Tamamura, Hidemitsu Harada, Hitoshi Nagatsuka
• Journal: Oral surgery, oral medicine, oral pathology and oral radiology (Oral Surg Oral Med Oral Pathol Oral Radiol) Vol. 114 Issue 6 Pg. 771-7 (Dec 2012) ISSN: 2212-4411 [Electronic] United States
• PMID: 23159115 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• DNA Primers
• Wnt Proteins
• Alkaline Phosphatase

Topics

• Alkaline Phosphatase (metabolism)
• Ameloblastoma (genetics)
• Base Sequence
• Blotting, Western
• DNA Primers
• Down-Regulation
• Humans
• Immunohistochemistry
• Jaw Neoplasms (genetics)
• Osteogenesis (genetics)
• Reverse Transcriptase Polymerase Chain Reaction
• Wnt Proteins (genetics)