DNA methyltransferase expression in odontogenic cysts and tumours

Cavaliéri Gomes,Carolina; Ricieri Brito,João A.; Andrade,Carlos I.; Gomes,Ricardo S.

doi:10.3892/ol_00000026

DNA methyltransferase expression in odontogenic cysts and tumours

Authors:
- Carolina Cavaliéri Gomes
- João A. Ricieri Brito
- Carlos I. Andrade
- Ricardo S. Gomes
View Affiliations

Affiliations: Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais, CEP 31270-901, Belo Horizonte, Brazil
Published online on: January 1, 2010 https://doi.org/10.3892/ol_00000026
Pages: 143-146

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Epigenetic silencing of gene expression by promoter CpG island hypermethylation is promoted by the enzymes, DNA methyltransferases (DNMTs). DNMT3a is mainly involved in de novo methylation, whereas DNMT1 acts mainly as a maintenance methyltransferase. The purpose of this study was to investigate the immunoexpression of DNMT1 and DNMT3a in a set of odontogenic cysts and tumours. Formalin-fixed and paraffin-embedded tissue samples of eight radicular cysts, 10 odontogenic keratocysts (OKC), eight adenomatoid odontogenic tumours (AOT), 16 ameloblastomas and eight samples of normal mucosae were included in the study. The DNMT1 and DNMT3a proteins were identified by using a highly sensitive polymer-based system. We found that the normal oral mucosa, OKC, AOT, radicular cyst and ameloblastomas samples showed a widespread nuclear and cytoplasmic immunopositivity for DNMT1. Some radicular cysts, ameloblastomas, AOT and OKC samples presented a positive cytoplasmic reaction for DNMT3a, while negative staining was observed in the normal oral mucosa. Nuclear positivity was found only in the suprabasal cell layers of three OKC samples. Our study shows an increased expression of DNMT3a in odontogenic cysts and tumours, confirming that epigenetic mechanisms are involved in the development of these tumours.

View Figures

View References

1	Shaw R: The epigenetics of oral cancer. Int J Oral Maxillofac Surg. 35:101–108. 2006. View Article : Google Scholar : PubMed/NCBI
2	Bestor TH and Ingram VM: Two DNA methyltransferases from murine erythroleukemia cells: purification, sequence specificity, and mode of interaction with DNA. Proc Natl Acad Sci USA. 80:5559–5563. 1983. View Article : Google Scholar : PubMed/NCBI
3	Okano M, Xie S and Li E: Cloning and characterization of a family of novel mammalian DNA (cytosine-5) methyltransferases. Nat Genet. 19:219–220. 1998. View Article : Google Scholar : PubMed/NCBI
4	Pradhan S, Bacolla A, Wells RD and Roberts RJ: Recombinant human DNA (cytosine-5) methyltransferase. I Expression, purification, and comparison of de novo and maintenance methylation. J Biol Chem. 274:33002–33010. 1999. View Article : Google Scholar : PubMed/NCBI
5	Ha PK and Califano JA: Promoter methylation and inactivation of tumour-suppressor genes in oral squamous-cell carcinoma. Lancet Oncol. 7:77–82. 2006. View Article : Google Scholar : PubMed/NCBI
6	Kautiainen TL and Jones PA: DNA methyltransferase levels in tumorigenic and nontumorigenic cells in culture. J Biol Chem. 261:1594–1598. 1986.PubMed/NCBI
7	Sun L, Hui AM, Kanai Y, Sakamoto M and Hirohashi S: Increased DNA methyltransferase expression is associated with an early stage of human hepatocarcinogenesis. Jpn J Cancer Res. 88:1165–1170. 1997. View Article : Google Scholar : PubMed/NCBI
8	De Marzo AM, Marchi VL, Yang ES, Veeraswamy R, Lin X and Nelson WG: Abnormal regulation of DNA methyltransferase expressing during colorectal carcinogenesis. Cancer Res. 59:3855–3860. 1999.PubMed/NCBI
9	Barreto DC, Gomez RS, Bale AE, Boson WL and De Marco L: PTCH gene mutations in odontogenic keratocysts. J Dent Res. 79:1418–1422. 2000. View Article : Google Scholar : PubMed/NCBI
10	Perdigão PF, Gomez RS, Pimenta FJGS and De Marco L: Ameloblastin gene (AMBN) mutations associated with epithelial odontogenic tumours. Oral Oncol. 40:841–846. 2004.PubMed/NCBI
11	Moreira PR, Guimarães MM, Guimarães ALS, Diniz MG, Gomes CC, Brito JAR and Gomez RS: Methylation of P16, P21, P27, RB1 and P53 genes in odontogenic keratocysts. J Oral Pathol Med. 38:99–103. 2009. View Article : Google Scholar : PubMed/NCBI
12	Robertson KD, Uzvolgyi E, Liang G, Talmadge C, Sumegi J, Gonzales FA and Jones PA: The human DNA methyltransferases (DNMTs) 1, 3a and 3b: coordinate mRNA expression in normal tissues and overexpression in neoplasms. Nucleic Acids Res. 27:2291–2298. 1999. View Article : Google Scholar : PubMed/NCBI
13	Etoh T, Kanai Y, Ushijima S, Nakagawa T, Nakanishi Y, Sasako M, Kitano S and Hirohashi S: Increased DNA methyltransferase 1 (DNMT1) protein expression correlates significantly with poorer tumour differentiation and frequent DNA hypermethylation of multiple CpG islands in gastric cancers. Am J Pathol. 164:689–699. 2004. View Article : Google Scholar : PubMed/NCBI
14	Peng DF, Kanai Y, Sawada M, Ushijima S, Hiraoka N, Kosuge T and Hirohashi S: Increased DNA methyltransferase 1 (DNMT1) protein expression in precancerous conditions and ductal carcinomas of the pancreas. Cancer Sci. 96:403–408. 2005. View Article : Google Scholar : PubMed/NCBI
15	Lee PJ, Washer LL, Law DJ, Boland CR, Horon IL and Feinberg AP: Limited up-regulation of DNA methyltransferase in human colon cancer reflecting increased cell proliferation. Proc Natl Acad Sci USA. 93:10366–10370. 1996. View Article : Google Scholar : PubMed/NCBI
16	Szyf M, Bozovic V and Tanigawa G: Growth regulation of mouse DNA methyltransferase gene expression. J Biol Chem. 266:10027–10030. 1991.PubMed/NCBI
17	Abiko Y, Nagayasu H, Takeshima M, Yamazaki M, Nishimura M, Kusano K, Kitajo H, Saitoh M, Kawakami T, Chiba I and Kaku T: Ameloblastic carcinoma ex ameloblastoma: report of a case-possible involvement of CpG island hypermethylation of the p16 gene in malignant transformation. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 103:72–76. 2007. View Article : Google Scholar : PubMed/NCBI
18	Choi MS, Shim YH, Hwa JY, Lee SK, Ro JY, Kim JS and Yu E: Expression of DNA methyltransferases in multistep hepatocarcinogenesis. Hum Pathol. 34:11–17. 2003. View Article : Google Scholar : PubMed/NCBI