C-Fos expression is a molecular predictor of progression and survival in epithelial ovarian carcinoma

Br J Cancer. 2008 Oct 21;99(8):1269-75. doi: 10.1038/sj.bjc.6604650.

Abstract

Members of the Fos protein family dimerise with Jun proteins to form the AP-1 transcription factor complex. They have a central function in proliferation and differentiation of normal tissue as well as in oncogenic transformation and tumour progression. We analysed the expression of c-Fos, FosB, Fra-1 and Fra-2 to investigate the function of Fos transcription factors in ovarian cancer. A total of 101 patients were included in the study. Expression of Fos proteins was determined by western blot analysis, quantified by densitometry and verified by immunohistochemistry. Reduced c-Fos expression was independently associated with unfavourable progression-free survival (20.6, 31.6 and 51.2 months for patients with low, moderate and high c-Fos expression; P=0.003) as well as overall survival (23.8, 46.0 and 55.5 months for low, moderate and high c-Fos levels; P=0.003). No correlations were observed for FosB, Fra-1 and Fra-2. We conclude that loss of c-Fos expression is associated with tumour progression in ovarian carcinoma and that c-Fos may be a prognostic factor. These results are in contrast to the classic concept of c-Fos as an oncogene, but are supported by the recently discovered tumour-suppressing and proapoptotic function of c-Fos in various cancer types.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis*
  • Blotting, Western
  • Disease Progression
  • Disease-Free Survival
  • Female
  • Fos-Related Antigen-2 / biosynthesis
  • Gene Expression
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Middle Aged
  • Neoplasms, Glandular and Epithelial / genetics
  • Neoplasms, Glandular and Epithelial / metabolism*
  • Neoplasms, Glandular and Epithelial / mortality
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / mortality
  • Prognosis
  • Proto-Oncogene Proteins c-fos / biosynthesis*

Substances

  • Biomarkers, Tumor
  • FOSB protein, human
  • FOSL2 protein, human
  • Fos-Related Antigen-2
  • Proto-Oncogene Proteins c-fos
  • fos-related antigen 1