Osteogenic genes related to the canonic WNT pathway are down-regulated in ameloblastoma

Sathi, G.A. and Tsujigiwa, H. and Ito, S. and Siar, C.H. and Katase, N. and Tamamura, R. and Harada, H. and Nagatsuka, H. (2012) Osteogenic genes related to the canonic WNT pathway are down-regulated in ameloblastoma. Oral Surgery Oral Medicine Oral Pathology Oral Radiology, 114 (6). pp. 771-777. ISSN 2212-4403, DOI https://doi.org/10.1016/j.oooo.2012.08.453.


Download (142kB)


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. (Oral Surg Oral Med Oral Pathol Oral Radiol 2012;114:771-777)

Item Type: Article
Additional Information: ISI Document Delivery No.: 041BA Times Cited: 0 Cited Reference Count: 33 Cited References: Barnes L, 2005, WORLD HEALTH ORGANIZ Bodine PVN, 2006, REV ENDOCR METAB DIS, V7, P33, DOI 10.1007/s11154-006-9002-4 Chen Y, 2007, J BIOL CHEM, V282, P526, DOI 10.1074/jbc.M602700200 Christine AF, 2011, DNA REPAIR ON THE PA, P255 DeVilliers P, 2011, J DENT RES, V90, P463, DOI 10.1177/0022034510391791 Etheridge SL, 2004, STEM CELLS, V22, P849, DOI 10.1634/stemcells.22-5-849 Gaur T, 2005, J BIOL CHEM, V280, P33132, DOI 10.1074/jbc.M500608200 Gori F, 2004, ENDOCRINOLOGY, V145, P1050, DOI 10.1210/en.2003-1314 Gori F, 2001, J BIOL CHEM, V276, P46515, DOI 10.1074/jbc.M105757200 Harada H, 1998, J ORAL PATHOL MED, V27, P207 Hu HL, 2005, DEVELOPMENT, V132, P49, DOI 10.1242/dev.01564 Kawano Y, 2003, J CELL SCI, V116, P2627, DOI 10.1242/jcs.00623 Krishnan V, 2006, J CLIN INVEST, V116, P1202, DOI 10.1172/JCI28551 Migaldi M, 2008, ORAL ONCOL, V44, P50, DOI 10.1016/j.oraloncology.2006.12.004 Nakagawa T, 2011, MOL CELL, V43, P381, DOI 10.1016/j.molce1.2011.05.033 NEER EJ, 1994, NATURE, V371, P297, DOI 10.1038/371297a0 Oshima T, 2005, BLOOD, V106, P3160, DOI 10.1182/blood-2004-12-4940 Pereira KMA, 2010, ORAL SURG ORAL MED O, V109, P425, DOI 10.1016/j.tripleo.2009.10.032 Rattner A, 1997, P NATL ACAD SCI USA, V94, P2859, DOI 10.1073/pnas.94.7.2859 Rodriguez AP, 2004, J HARD TISSUES BIOL, V13, P91 Rodriguez AP, 2007, J HARD TISSUE BIOL, V16, P1, DOI 10.2485/jhtb.16.1 Sathi GA, 2009, ORAL ONCOL, V45, P856, DOI 10.1016/j.oraloncology.2009.02.001 Sathi Gul San Ara, 2007, J Oral Pathol Med, V36, P609 Sathi GSA, 2008, HISTOPATHOLOGY, V53, P458, DOI 10.1111/j.1365-2559.2008.03127.x Siar CH, 2012, J ORAL PATHOL MED, V41, P332, DOI 10.1111/j.1600-0714.2011.01104.x Sierra J, 2006, GENE DEV, V20, P586, DOI 10.1101/gad.1385806 Smith TF, 1999, TRENDS BIOCHEM SCI, V24, P181, DOI 10.1016/S0968-0004(99)01384-5 Sukarawan W, 2010, AM J PATHOL, V176, P461, DOI 10.2353/ajpath.2010.090478 Tanahashi J, 2008, J ORAL PATHOL MED, V37, P565, DOI 10.1111/j.1600-0714.2008.00645.x UMEZAWA A, 1992, J CELL PHYSIOL, V151, P197, DOI 10.1002/jcp.1041510125 Wenig BM, 2008, ATLAS HEAD NECK PATH, P131 Zhou HB, 2009, EXP CELL RES, V315, P2953, DOI 10.1016/j.yexcr.2009.07.030 Zhu ED, 2008, J BIOL CHEM, V283, P7361, DOI 10.1074/jbc.M703304200 Sathi, Gulsan A. Tsujigiwa, Hidetsugu Ito, Satoshi Siar, Chong Huat Katase, Naoki Tamamura, Ryo Harada, Hidemitsu Nagatsuka, Hitoshi Japanese Ministry of Education, Culture, Sports, Science, and Technology (MEXT) 22791766, 24592766; University of Malaya RG394/11HTM Supported by a Grant-in-Aid for Research (C) (no. 24592766) and Grant-in-Aid for Young Scientists (B) (no. 22791766) from the Japanese Ministry of Education, Culture, Sports, Science, and Technology (MEXT) and by the University of Malaya (RG394/11HTM). Elsevier science inc New york
Uncontrolled Keywords: wd-40 repeat protein beta-catenin bone-formation signaling pathway wd-repeat cell-line expression differentiation induce family
Subjects: R Medicine > RK Dentistry
Divisions: Faculty of Dentistry > Dept of Oral Pathology & Oral Medicine & Periodontology
Depositing User: Mr Ahmad Azwan Azman
Date Deposited: 19 Apr 2013 00:04
Last Modified: 19 Apr 2013 00:04
URI: http://eprints.um.edu.my/id/eprint/5837

Actions (login required)

View Item View Item