O6-methylguanine-DNA methyltransferase in equine sarcoids: molecular and epigenetic analysis

BMC Veterinary Research

Research Article

Franco Roperto¹  Annunziata Corteggio¹  Gennaro Altamura¹  Giuseppe Borzacchiello¹  Maria Strazzullo²  Romina Francioso³  Maurizio D'Esposito⁴ 

[1] Department of Pathology and Animal health, University of Naples Federico II, Via Veterinaria, 1-80137, Napoli, Italy;Institute for Animal Production System in Mediterranean Environment, National Research Council, Via Argine, 1085 80147, Naples, Italy;Institute of Genetic and Biophysics ABT, National Research Council, Via P.Castellino 111, 80131, Naples, Italy;Institute of Genetic and Biophysics ABT, National Research Council, Via P.Castellino 111, 80131, Naples, Italy;IRCCS Neuromed, Pozzilli, Italy;

关键词: BPV;    Equine sarcoid;    MGMT;   

DOI  :  10.1186/1746-6148-8-218

 received in 2012-08-01, accepted in 2012-11-06,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundBovine papillomaviruses (BPVs) types 1 and 2 are the only known papillomaviruses able to jump the species. In fact, BPVs 1/2 induce neoplasia in their natural bovine host but infection is also associated to neoplastic skin lesions in equids termed sarcoids. The equine sarcoid is considered to be the most common equine cutaneous tumour worldwide for which no effective therapy is available. Very little is known about the molecular mechanisms underlying tumourigenesis, although genes contributing to sarcoid development have been identified. Several studies associate the development of cancer to the loss of function of a number of oncosuppressor genes. In this study the putative role of O6-methylguanine-DNA methyltrasferase (MGMT) was investigated for sarcoids. The expression of the oncosuppressor protein was assessed in normal and sarcoid cells and tissues. In addition, the DNA methylation profile was analysed to assess the role of epigenetic mechanism in regulation of MGMT expression.ResultsA group of 15 equine sarcoids and two primary sarcoid cell lines (fibroblasts) were analyzed for the expression of MGMT protein by immunohistochemistry, immunofluorescence and Western blotting techniques. The sarcoid cell line EqSO4b and the tumour samples showed a reduction or absence of MGMT expression. To investigate the causes of deregulated MGMT expression, ten samples were analyzed for the DNA methylation profile of the CpG island associated to the MGMT promoter. The analysis of 73 CpGs encompassing the region of interest showed in 1 out of 10 (10%) sarcoids a pronouncedly altered methylation profile when compared to the control epidermal sample. Similarily the EqSO4b cell line showed an altered MGMT methylation pattern in comparison to normal fibroblasts.ConclusionAs previously demonstrated for the oncosuppressor gene FHIT, analysis of MGMT expression in sarcoid tissues and a sarcoid-derived fibroblast cell line further suggests that oncosuppressor silencing may be also involved in BPV-induced equine tumours. Abnormal DNA methylation seems to be one of the possible molecular mechanisms involved in the alteration of MGMT expression. Further studies are required to address other basic molecular mechanisms involved in reduced MGMT expression. This study underlines the possible role of DNA methylation in oncosuppressor inactivation in equine sarcoids.

【 授权许可】

Unknown   
© Altamura et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.