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Open Access Research article

Epigenetic regulation of matrix metalloproteinase expression in ameloblastoma

Lucyana Conceição Farias1, Carolina Cavaliéri Gomes2, Marcela Carolina Rodrigues1, Wagner Henriques de Castro1, Júlio César Tanos Lacerda3, Efigênia Ferreira e Ferreira4 and Ricardo Santiago Gomez1*

Author Affiliations

1 Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais, Av. Antonio Carlos, 6627, CEP 31270 901 , Belo Horizonte, Minas Gerais, Brazil

2 Department of Pathology, Biological Sciences Institute, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil

3 Department of Oral Surgery and Diagnosis, Odilon Behrens Hospital, Belo Horizonte, Brazil

4 Department of Social and Preventive Dentistry, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil

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BMC Clinical Pathology 2012, 12:11  doi:10.1186/1472-6890-12-11

Published: 6 August 2012

Abstract

Background

An ameloblastoma is a benign odontogenic neoplasm with aggressive behaviour and high recurrence rates. The increased expression of matrix metalloproteinases (MMPs) has been reported in ameloblastomas. In the present study, we hypothesised that epigenetic alterations may regulate MMP expression in ameloblastomas.

Methods

We investigated the methylation status of the genes MMP-2 and MMP-9 in addition to mRNA transcription and protein expression in ameloblastomas. Methylation analysis was performed by both methylation-specific polymerase chain reaction (MSP-PCR) and restriction enzyme digestion to evaluate the methylation profile of MMP-2 and MMP-9 in 12 ameloblastoma samples and 12 healthy gingiva fragments, which were included as controls. Furthermore, we investigated the transcription levels of the genes by quantitative reverse-transcription PCR (qRT-PCR). Zymography was performed to verify protein expression in ameloblastomas.

Results

The ameloblastomas showed a high frequency of unmethylated MMP-2 and MMP-9, whereas the healthy gingival samples presented a sharp prevalence of methylated MMPs. Higher expression levels of MMP-9 were found in ameloblastomas compared to healthy gingiva. However, no significant differences in the MMP-2 mRNA expression between groups was found. All ameloblastomas showed positive expression of MMP-2 and MMP-9 proteins.

Conclusions

Our findings suggest that expression of MMP-9 is increased in ameloblastomas and is possibly modulated by unmethylation of the gene.

Keywords:
Ameloblastoma; Odontogenic tumours; Matrix metalloproteinases; MMP-2; MMP-9; Methylation; Epigenetic