ROLE OF E2F-1 IN CHEMOSENSITIVITY

The E2F family of transcription factors, in partnership with DP protei ns, is thought to regulate transcription of genes that encode protein products that are required for DNA synthesis, which include important cancer chemotherapeutic targets such as thymidylate synthase and dihyd rofolate reductase. This study was conducted to investigate the effect s of overexpression of human E2F-1 cDNA on chemosensitivity in a human fibrosarcoma cell line, HT-1080. The E2F-1-overexpressing HT-1080 cel ls had a shorter doubling time both in vitro and in vivo. Associated w ith an up-regulation of TS, E2F-1-transfected cells were more resistan t to alorouracil than were untransfected cells. These E2F-1 transfecta nts, although resistant to fluoropyrimidines and serum deprivation, we re more sensitive to etoposide, doxorubicin, and SN38 (thc active meta bolite of irinotecan) but not to Taxol.