Banerjee D, Schnieders B, Fu J Z, Adhikari D, Zhao S C, Bertino J R
Molecular Pharmacology and Experimental Therapeutics Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA.
Cancer Res. 1998 Oct 1;58(19):4292-6.
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.
转录因子E2F家族与DP蛋白协同作用，被认为可调节那些编码DNA合成所需蛋白质产物的基因的转录，这些蛋白质产物包括重要的癌症化疗靶点，如胸苷酸合成酶和二氢叶酸还原酶。本研究旨在调查人E2F-1 cDNA过表达对人纤维肉瘤细胞系HT-1080化学敏感性的影响。过表达E2F-1的HT-1080细胞在体外和体内的倍增时间均较短。与胸苷酸合成酶上调相关，转染E2F-1的细胞比未转染细胞对5-氟尿嘧啶更具抗性。这些E2F-1转染子虽然对氟嘧啶和血清剥夺具有抗性，但对依托泊苷、阿霉素和SN38（伊立替康的活性代谢物）更敏感，而对紫杉醇不敏感。
