Abstract
BackgroundAn 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.MethodsWe 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.ResultsThe 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.ConclusionsOur findings suggest that expression of MMP-9 is increased in ameloblastomas and is possibly modulated by unmethylation of the gene.
Highlights
An ameloblastoma is a benign odontogenic neoplasm with aggressive behaviour and high recurrence rates
As matrix metalloproteinases (MMPs) may be regulated by DNA methylation in malignant neoplasms [18,19], such phenomenon might be important in ameloblastoma pathogenesis and should be investigated
An increased frequency of unmethylated MMP-9 of specific CG sites digested by HhaI was identified in the ameloblastomas
Summary
An ameloblastoma is a benign odontogenic neoplasm with aggressive behaviour and high recurrence rates. An ameloblastoma is a benign odontogenic tumour that exhibits a high recurrence risk, aggressive behaviour and local invasiveness [1]. Matrix metalloproteinases (MMPs) are zinc-dependent enzymes that are important in extracellular matrix remodelling and are associated with tumour growth and invasion through collagen matrix degradation [11]. The invasive characteristic of ameloblastomas has been associated with the expression of genes related to bone turnover and extracellular matrix remodelling; these include BMP, RANKL and its receptor, MMP and TIMP [12,13,14,15,16,17]. As MMPs may be regulated by DNA methylation in malignant neoplasms [18,19], such phenomenon might be important in ameloblastoma pathogenesis and should be investigated. The purpose of this study was to investigate the association between MMP-2 and MMP-9 methylation and their mRNA transcription and protein expression in ameloblastomas
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