Role of E2F-1 in chemosensitivity.
The E2F family of transcription factors, in partnership with DP proteins, 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 dihydrofolate reductase. This study was conducted to investigate the effects of overexpression of human E2F-1 cDNA on chemosensitivity in a human fibrosarcoma cell line, HT-1080. The E2F-1-overexpressing HT-1080 cells had a shorter doubling time both in vitro and in vivo. Associated with an up-regulation of TS, E2F-1-transfected cells were more resistant to 5-fluorouracil than were untransfected cells. These E2F-1 transfectants, although resistant to fluoropyrimidines and serum deprivation, were more sensitive to etoposide, doxorubicin, and SN38 (the active metabolite of irinotecan) but not to Taxol.
Molecular Pharmacology and Experimental Therapeutics Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA.
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D
Banerjee
B
B
Schnieders
J Z
JZ
Fu
D
D
Adhikari
S C
SC
Zhao
J R
JR
Bertino
D000964:Antimetabolites, Antineoplastic / Q000633:toxicity; D000970:Antineoplastic Agents / Q000633:toxicity*; D000972:Antineoplastic Agents, Phytogenic / Q000633:toxicity; D002166:Camptothecin / Q000031:analogs & derivatives / Q000633:toxicity; D002352:Carrier Proteins; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D002455:Cell Division; D002470:Cell Survival / Q000187:drug effects; D003001:Cloning, Molecular; D016895:Culture Media, Serum-Free; D004268:DNA-Binding Proteins / Q000378:metabolism; D004317:Doxorubicin / Q000633:toxicity; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D005047:Etoposide / Q000633:toxicity; D005354:Fibrosarcoma; D006801:Humans; D000077146:Irinotecan; D017239:Paclitaxel / Q000633:toxicity; D011994:Recombinant Proteins / Q000378:metabolism; D056465:Retinoblastoma-Binding Protein 1; D013762:Tetrahydrofolate Dehydrogenase / Q000378:metabolism; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured
D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D016895:Culture Media, Serum-Free; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D011994:Recombinant Proteins; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors; D005047:Etoposide; D000077146:Irinotecan; D004317:Doxorubicin; D013762:Tetrahydrofolate Dehydrogenase; D017239:Paclitaxel; D002166:Camptothecin