Overexpression of Fra-1, c-Jun and c-Fos in odontogenic keratocysts: potential correlation with proliferative and anti-apoptotic activity

Histopathology. 2018 Dec;73(6):933-942. doi: 10.1111/his.13705. Epub 2018 Nov 4.

Abstract

Aims: The purpose of this study was to explore the potential involvement of Fra-1, c-Jun and c-Fos, three vital members of the AP-1 complex, in the pathogenesis of odontogenic keratocysts (OKCs).

Methods and results: Tissue samples, containing 10 normal oral mucosa (OM), 10 dentigerous cysts (DC) and 32 OKC specimens, were applied to investigate the expression levels of Fra-1, c-Jun and c-Fos by immunohistochemistry and real-time-quantitative polymerase chain reaction (RT-qPCR). The association between Fra-1, c-Jun and c-Fos expression levels and markers of proliferation [Ki-67, proliferating cell nuclear antigen (PCNA)], anti-apoptosis (Bcl-2) was then investigated in the OKC serial tissue sections. The results showed that Fra-1, c-Jun and c-Fos expression levels were increased significantly in OKCs compared to these in OM and DC tissue samples. Meanwhile, the expression levels of Fra-1, c-Jun and c-Fos were associated positively with the expression levels of Ki-67, PCNA and Bcl-2, as confirmed further by double-labelling immunofluorescence analysis and hierarchical analysis.

Conclusions: This study revealed for the first time that Fra-1, c-Jun and c-Fos were overexpressed in OKCs and had a close correlation with proliferation and anti-apoptosis potential of OKCs.

Keywords: AP-1; apoptosis; odontogenic keratocysts; proliferation.

MeSH terms

  • Apoptosis / physiology*
  • Cell Proliferation / physiology*
  • Humans
  • Immunohistochemistry
  • Mouth Mucosa / metabolism*
  • Mouth Mucosa / pathology
  • Odontogenic Cysts / metabolism*
  • Odontogenic Cysts / pathology
  • Proto-Oncogene Proteins c-fos / metabolism*
  • Proto-Oncogene Proteins c-jun / metabolism*

Substances

  • Proto-Oncogene Proteins c-fos
  • Proto-Oncogene Proteins c-jun
  • fos-related antigen 1