C-Fos expression is a molecular predictor of progression and survival in epithelial ovarian carcinoma.
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.
Department of Gynecology and Gynecologic Oncology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany. s.mahner@uke.uni-hamburg.de
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Mahner
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Baasch
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Schwarz
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Hein
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Wölber
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Jänicke
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Milde-Langosch
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D051921:Fos-Related Antigen-2 / Q000096:biosynthesis; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D011379:Prognosis; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D000099169:Fos-Related Antigen 1
D014408:Biomarkers, Tumor; D051921:Fos-Related Antigen-2; D016760:Proto-Oncogene Proteins c-fos; D000099169:Fos-Related Antigen 1; C064269:FOSB protein, human; C497872:FOSL2 protein, human