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BMC veterinary research2012; 8; 218; doi: 10.1186/1746-6148-8-218

O(6)-methylguanine-DNA methyltransferase in equine sarcoids: molecular and epigenetic analysis.

Abstract: Bovine 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. Results: A 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. Conclusions: As 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.
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Publication Date: 2012-11-10 PubMed ID: 23140380PubMed Central: PMC3512464DOI: 10.1186/1746-6148-8-218Google Scholar: Lookup
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Summary

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The research article explores the role of a specific oncosuppressor gene, O6-methylguanine-DNA methyltransferase (MGMT), in equine sarcoids – a common type of skin tumor in horses caused by certain types of Bovine Papillomaviruses. The scientists found abnormal DNA methylation affecting MGMT expression, suggesting this as one potential mechanism behind the development of these tumours.

Understanding Equine Sarcoids and the Study’s Aims

  • The research focused on equine sarcoids, skin tumours in horses which are found globally and currently have no effective treatment. These tumors are believed to be induced by Bovine Papillomaviruses (BPVs) types 1 and 2, viruses usually infecting cattle but capable of crossing species boundaries.
  • While some contributing genes have been identified, the molecular mechanisms underlying the formation of these tumors are not well understood. Previous research suggested the potential role of oncosuppressor genes, genes that prevent the process of tumourigenesis, being turned off or “silenced”.
  • The present study aimed to explore the potential role of one such oncosuppressor, O6-methylguanine-DNA methyltransferase (MGMT), in the development of equine sarcoids. The researchers sought to analyze MGMT expression in both normal and sarcoid cells and tissues, and determine if epigenetic mechanisms, particularly DNA methylation, affect this expression.

Testing Procedure

  • The scientists used a group of 15 equine sarcoids and two primary sarcoid cell lines (fibroblasts) to study the expression of MGMT via techniques like immunohistochemistry, immunofluorescence, and Western blotting.
  • They found that in both the sarcoid cell line EqSO4b and the tumor samples, MGMT expression was reduced or absent.
  • An analysis on the DNA methylation profile of the CpG island tied to the MGMT promoter was conducted on ten samples. Results showed a pronouncedly altered methylation pattern in one of the samples, providing possible evidence of MGMT expression being regulated epigenetically.

Key Findings

  • The results suggest that MGMT could be one of the oncosuppressors affected in BPV-induced equine tumours and that abnormal DNA methylation could be one of the underlying molecular mechanisms affecting this expression.
  • This builds upon earlier work demonstrating similar consequences for another oncosuppressor gene, FHIT.
  • However, further research is needed to confirm these findings and explore any other molecular mechanisms that could be involved in reducing MGMT expression.

Cite This Article

APA
Altamura G, Strazzullo M, Corteggio A, Francioso R, Roperto F, D'Esposito M, Borzacchiello G. (2012). O(6)-methylguanine-DNA methyltransferase in equine sarcoids: molecular and epigenetic analysis. BMC Vet Res, 8, 218. https://doi.org/10.1186/1746-6148-8-218

Publication

BMC veterinary research
ISSN: 1746-6148
NlmUniqueID: 101249759
Country: England
Language: English
Volume: 8
Pages: 218

Researcher Affiliations

Altamura, Gennaro
  • Department of Pathology and Animal health, University of Naples Federico II, Via Veterinaria, 1-80137, Napoli, Italy.
Strazzullo, Maria
    Corteggio, Annunziata
      Francioso, Romina
        Roperto, Franco
          D'Esposito, Maurizio
            Borzacchiello, Giuseppe

              MeSH Terms

              • Animals
              • Bovine papillomavirus 1
              • Cell Line, Tumor
              • CpG Islands
              • DNA Methylation
              • Down-Regulation
              • Gene Expression Regulation, Enzymologic
              • Gene Expression Regulation, Neoplastic / physiology
              • Horse Diseases / metabolism
              • Horses
              • O(6)-Methylguanine-DNA Methyltransferase / genetics
              • O(6)-Methylguanine-DNA Methyltransferase / metabolism
              • Promoter Regions, Genetic
              • Skin Neoplasms / metabolism
              • Skin Neoplasms / veterinary
              • Skin Neoplasms / virology

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              Citations

              This article has been cited 2 times.
              1. Pawlina-Tyszko K, Semik-Gurgul E, Ząbek T, Witkowski M. Methylation Status of Gene Bodies of Selected microRNA Genes Associated with Neoplastic Transformation in Equine Sarcoids. Cells 2022 Jun 14;11(12).
                doi: 10.3390/cells11121917pubmed: 35741046google scholar: lookup
              2. Monteiro MM, de Castro ELA, Pereira AJM, Thiesen R, Thiesen RMC, Salvarani FM. BCG Immunotherapy in Equine Sarcoid Treatment: Mechanisms, Clinical Efficacy, and Challenges in Veterinary Oncology. Viruses 2025 Sep 29;17(10).
                doi: 10.3390/v17101322pubmed: 41157593google scholar: lookup
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