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BMC veterinary research2012; 8; 30; doi: 10.1186/1746-6148-8-30

Molecular and epigenetic analysis of the fragile histidine triad tumour suppressor gene in equine sarcoids.

Abstract: Sarcoids are peculiar equine benign tumours. Their onset is associated with Bovine Papillomavirus type -1 or -2 (BPV-1/2) infection. Little is known about the molecular interplay between viral infection and neoplastic transformation. The data regarding papillomavirus infections in human species show the inactivation of a number of tumour suppressor genes as basic mechanism of transformation. In this study the putative role of the tumour suppressor gene Fragile Histidine Triad (FHIT) in sarcoid tumour was investigated in different experimental models. The expression of the oncosuppressor protein was assessed in normal and sarcoid cells and tissue. Results: Nine paraffin embedded sarcoids and sarcoid derived cell lines were analysed for the expression of FHIT protein by immunohistochemistry, immunofluorescence techniques and western blotting. These analyses revealed the absence of signal in seven out of nine sarcoids. The two sarcoid derived cell lines too showed a reduced signal of the protein. To investigate the causes of the altered protein expression, the samples were analysed for the DNA methylation profile of the CpG island associated with the FHIT promoter. The analysis of the 32 CpGs encompassing the region of interest showed no significative differential methylation profile between pathological tissues and cell lines and their normal counterparts. Conclusions: This study represent a further evidence of the role of a tumour suppressor gene in equine sarcoids and approaches the epigenetic regulation in this well known equine neoplasm. The data obtained in sarcoid tissues and sarcoid derived cell lines suggest that also in horse, as in humans, there is a possible involvement of the tumour suppressor FHIT gene in BPV induced tumours. DNA methylation seems not to be involved in the gene expression alteration. Further studies are needed to understand the basic molecular mechanisms involved in reduced FHIT expression.
Publication Date: 2012-03-16 PubMed ID: 22424615PubMed Central: PMC3361464DOI: 10.1186/1746-6148-8-30Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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The research studied the relationship between the tumor suppressor gene Fragile Histidine Triad (FHIT) and the development of sarcoid tumors in horses, which are commonly associated with bovine papillomavirus infection. The study found a possible involvement of the FHIT gene in sarcoid formation, though further investigations are needed to understand the molecular mechanisms involved in this gene expression alteration.

Research Context and Methods

  • Sarcoid tumors in horses are benign growths often associated with Bovine Papillomavirus type -1 or -2 (BPV-1/2) infection.
  • The study aimed to explore the involvement of the tumor suppressor gene Fragile Histidine Triad (FHIT) in sarcoid tumor development. Previous research on papillomavirus infections in humans showed the inactivation of several tumor suppressor genes as the basic mechanism of transformation.
  • The study utilized different experimental models, examining FHIT levels in normal, sarcoid cells and tissues. FHIT was analyzed through immunohistochemistry, immunofluorescence techniques and western blotting in nine paraffin-embedded sarcoids and sarcoid cell lines.

Results and Findings

  • The researchers discovered that the expression of FHIT, an oncosuppressor protein, was absent in seven out of nine sarcoids and showed reduced levels in the sarcoid cell lines. This suggests that the absence or reduction of FHIT may be associated with the development of sarcoid tumors.
  • The team also investigated whether changes in DNA methylation, an epigenetic mechanism that can regulate gene expression, could explain the altered protein expression.
  • However, no significant differential methylation profile was found in the pathological tissues and cell lines compared to their normal counterparts. This indicates that, contrary to the researchers’ expectations, DNA methylation does not play a role in gene expression alteration of FHIT in sarcoids.

Conclusions and Further Research

  • This study added evidence to the role of the FHIT tumour suppressor gene in equine sarcoids, contributing to the understanding of the neoplasm’s epigenetic regulation.
  • A crucial finding is the potential involvement of the FHIT suppressor gene in BPV-induced tumors, echoing similar processes in humans.
  • Despite these findings, the underlying molecular mechanisms leading to reduced FHIT expression remain unclear and necessitate further exploration. This knowledge gap highlights the need for continued research into the pathological pathways involved in equine sarcoid tumors, particularly concerning the role of tumor suppressor genes.

Cite This Article

APA
Strazzullo M, Corteggio A, Altamura G, Francioso R, Roperto F, D'Esposito M, Borzacchiello G. (2012). Molecular and epigenetic analysis of the fragile histidine triad tumour suppressor gene in equine sarcoids. BMC Vet Res, 8, 30. https://doi.org/10.1186/1746-6148-8-30

Publication

ISSN: 1746-6148
NlmUniqueID: 101249759
Country: England
Language: English
Volume: 8
Pages: 30

Researcher Affiliations

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

              MeSH Terms

              • Acid Anhydride Hydrolases / genetics
              • Acid Anhydride Hydrolases / metabolism
              • Age Factors
              • Animals
              • Bovine papillomavirus 1 / genetics
              • Bovine papillomavirus 1 / metabolism
              • Cell Line, Tumor
              • Epigenomics / standards
              • Gene Expression Regulation, Neoplastic
              • Horse Diseases / genetics
              • Horse Diseases / metabolism
              • Horse Diseases / virology
              • Horses
              • Immunohistochemistry / veterinary
              • Neoplasm Proteins / genetics
              • Neoplasm Proteins / metabolism
              • Papillomavirus Infections / genetics
              • Papillomavirus Infections / metabolism
              • Papillomavirus Infections / veterinary
              • Papillomavirus Infections / virology
              • RNA, Neoplasm / chemistry
              • RNA, Neoplasm / genetics
              • Reverse Transcriptase Polymerase Chain Reaction / veterinary
              • Skin Neoplasms / genetics
              • Skin Neoplasms / metabolism
              • Skin Neoplasms / veterinary
              • Skin Neoplasms / virology

              References

              This article includes 37 references

              Citations

              This article has been cited 1 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