The molecular and genetic characteristics of ameloblastoma are still poorly understood. We analyzed gene expression in fresh-frozen ameloblastomas and human fetal tooth germs, using a cDNA microarray. Thirty-four genes exhibited significant changes in expression levels in the ameloblastoma. Eleven genes were overexpressed more than three-fold, and 23 genes were underexpressed to below 0.4 of the control level. The oncogene FOS was the most overexpressed gene (from eight- to 14-fold), followed by tumor-necrosis-factor-receptor 1 (TNFRSF1A). Genes for sonic hedgehog (SHH), TNF-receptor-associated-factor 3 (TRAF3), rhoGTP-ase-activating protein 4 (ARHGAP4), deleted in colorectal carcinoma (DCC), cadherins 12 and 13 (CDH12 and 13), teratocarcinoma-derived growth-factor-1 (TDGF1), and transforming growth-factor-ß1 (TGFB1) were underexpressed in all tumors. In selected genes, a comparison between cDNA microarray and real-time RT-PCR confirmed similar relative gene expression changes. The gene expression profile identifies candidate genes that may be involved in the origination of ameloblastoma and several genes previously unidentified in relation to human tooth development.
Get full access to this article
View all access options for this article.
References
1.
Barreto DC, Gomez RS, Bale AE, Boson WL, De Marco L -2000-. PTCH gene mutations in odontogenic keratocysts. J Dent Res79:1418–1422.
2.
Baud V, Karin M -2001-. Signal transduction by tumor necrosis factor and its relatives. Trends Cell Biol11:372–377.
3.
Bessho Y, Miyoshi G, Sakata R, Kageyama R -2001-. Hes7: a bHLH-type repressor gene regulated by Notch and expressed in the presomitic mesoderm. Genes Cells6:175–185.
4.
Blobe GC, Schiemann WP, Lodish HF -2000-. Role of transforming growth factor beta in human disease. N Engl J Med342:1350–1358.
5.
Duggan DJ, Bittner M, Chen Y, Meltzer P, Trent JM -1999-. Expression profiling using cDNA microarrays. Nat Genet21:10–14.
6.
Gamberi G, Benassi MS, Böhling T, Ragazzini P, Molendini L, Sollazzo MR, et al. -1998-. C-myc and c-fos in human osteosarcoma: prognostic value of mRNA and protein expression. Oncology55:556–563.
7.
Gorrin Rivas MJ, Arii S, Furutani M, Harada T, Mizumoto M, Nishiyama H, et al. -1998-. Expression of human macrophage metalloelastase gene in hepatocellular carcinoma: correlation with angiostatin generation and its clinical significance. Hepatology28:986–993.
8.
Grigoriadis AE, Wang ZQ, Cecchini MG, Hofstetter W, Felix R, Fleisch HA, et al. -1994-. C-Fos: a key regulator of osteoclast-macrophage lineage determination and bone remodeling. Science266:443–448.
9.
Ha HY, Moon HB, Nam MS, Lee JW, Ryoo ZY, Lee TH, et al. -2001-. Overexpression of membrane-type matrix metalloproteinase-1 gene induces mammary gland abnormalities and adenocarcinoma in transgenic mice. Cancer Res61:984–990.
10.
Hardcastle Z, Mo R, Hui CC, Sharpe PT -1998-. The Shh signalling pathway in tooth development: defects in Gli2 and Gli3 mutants. Development125:2803–2811.
11.
Haufe CC, Eismann U, Deppisch RM, Stein G -2001-. Expression of beta2-microglobulin and c-fos mRNAs: is there an influence of high-or low-flux dialyzer membranes ? Kidney Int78-Suppl-:177–181.
12.
Heikinheimo K -1993-. Cell growth and differentiation of developing and neoplastic odontogenic tissues -dissertation-. Turku, Finland: Univ. of Turku.
13.
Jääskeläinen K, Jee KJ, Leivo I, Saloniemi I, Knuutila S, Heikinheimo K -2002-. Cell proliferation and chromosomal changes in human ameloblastoma. Cancer Genet Cytogenet -in press-.
14.
Jacobs TW, Byrne C, Colditz G, Connolly JL, Schnitt SJ -1999-. Radial scars in benign breast-biopsy specimens and the risk of breast cancer. N Engl J Med340:430–436.
15.
Jernvall J, Thesleff I -2000-. Reiterative signaling and patterning during mammalian tooth morphogenesis. Mech Dev92:19–29.
16.
Kawamura-Kodama K, Tsutsui J, Suzuki ST, Kanzaki T, Ozawa M -1999-. N-cadherin expressed on malignant T cell lymphoma cells is functional, and promotes heterotypic adhesion between the lymphoma cells and mesenchymal cells expressing N-cadherin. J Invest Dermatol112:62–66.
17.
Kramer IRH, Pindborg JJ, Shear M -1992-. World Health Organization. International classification of tumours: histological typing of odontogenic tumors. 2nd ed. Heidelberg, Germany: Springer-Verlag.
18.
Laurikkala J, Mikkola M, Mustonen T, Åberg T, Koppinen P, Pispa J, et al. -2001-. TNF signaling via the ligand-receptor pair ectodysplasin and edar controls the function of epithelial signaling centers and is regulated by Wnt and activin during tooth organogenesis. Dev Biol229:443–455.
19.
Lench NJ, Telford EA, High AS, Markham AF, Wicking C, Wainwright BJ -1997-. Characterisation of human patched germ line mutations in naevoid basal cell carcinoma syndrome. Hum Genet100:497–502.
Monreal AW, Ferguson BM, Headon DJ, Street SL, Overbeek PA, Zonana J -1999-. Mutations in human homologue of mouse dl cause autosomal recessive and dominant hypohidrotic ectodermal dysplasia. Nat Genet22:366–369.
22.
Nieminen P, Pekkanen M, Åberg T, Thesleff I -1998-. A graphical WWW-database on gene expression in tooth. Eur J Oral Sci106-Suppl 1-:7–11.
23.
Pepper MS -1997-. Transforming growth factor-beta: vasculogenesis, angiogenesis, and vessel wall integrity. Cytokine Growth Factor Rev8:21–43.
24.
Pishvaian MJ, Feltes CM, Thompson P, Bussemakers MJ, Schalken JA, Byers SW -1999-. Cadherin-11 is expressed in invasive breast cancer cell lines. Cancer Res59:947–952.
25.
Ross DT, Scherf U, Eisen MB, Perou CM, Rees C, Spellman P, et al. -2000-. Systemic variation in gene expression patterns in human cancer cell lines. Nat Genet24:227–235.
26.
Sato H, Seiki M -1996-. Membrane-type matrix metalloproteinases -MT-MMPs- in tumor metastasis. J Biochem119:209–215.
27.
Sharma SC, Richards JS -2000-. Regulation of AP1 -Jun/Fos- factor expression and activation in ovarian granulosa cells. Relation of JunD and Fra2 to terminal differentiation. J Biol Chem275:33718–33728.
28.
Shuttleworth CA -1997-. Type VIII collagen. Int J Biochem Cell Biol29:1145–1148.
29.
Todd R, Wong DT -2002-. DNA hybridization arrays for gene expression analysis of human oral cancer. J Dent Res81:89–97.
30.
Vickers RA, Gorlin RJ -1970-. Ameloblastoma: delineation of early histopathologic features of neoplasia. Cancer26:699–710.
