The Role of the c-fos Oncogene in Cisplatin Resistance

The c-fos oncogene has been proposed to play an important role not only in DNA synthesis (1) but also in resistance to the antineoplastic agent cis-diamminedichloroplatinum (cisplatin) (2). Administration of cisplatin to A2780 ovarian carcinoma cells was followed by a sequential induction of c-fos, dTMP synthase, and DNA polymerase. A2780 cells transfected with a plasmid containing the fos gene displayed morphological and pharmacological changes reflecting cisplatin resistance. A ribozyme (catalytic RNA) was designed to cleave c-fos mRNA. Cleavage conditions were optimized in vitro, and DNA encoding the fos ribozyme was cloned into the pMAMneo expression vector. The resultant plasmid was transfected into the A2780DDP cell line resistant to cisplatin, and the transformants assayed for enhanced sensitivity to cisplatin. These results suggest that c-fos plays a causal role in cisplatin resistance.