title: Activation of the human multidrug resistance-1 (mdr1) gene promoter in response to inhibitors of DNA topoisomerases.
abstract: The multidrug resistance (MDR1) gene encodes a Mr 170,000 energy-dependent membrane efflux pump termed P-glycoprotein, and the P-glycoprotein is often expressed in various human tumors before and after cancer chemotherapy. In this study, we have established a human cancer KB cell line (Kst-6) which stably expressed the CAT gene (pMDRCAT1) driven by the human MDR1 promoter. Exposure to inhibitors of DNA topoisomerase I (camptothecin: CPT-11) and II (etoposide: VP-16 and teniposide: VM-26) could efficiently induce CAT activities in both time- and dose-dependent manners. However, CAT activity could not be significantly induced when treated with an ATP-antagoist, novobiocin. Northern blot analysis showed about 5-fold increase in CAT mRNA levels in Kst-6 cells treated with CPT-11 or VP-16, but not with novobiocin. Proximal MDR1 promoter-binding activities of transacting factor were augmented in nuclear extracts from KB cells treated with CPT-11, VM-26, and VP-16.
authors.forename: K
authors.initials: K
authors.lastname: Kohno
authors.forename: S
authors.initials: S
authors.lastname: Sato
authors.forename: T
authors.initials: T
authors.lastname: Uchiumi
authors.forename: H
authors.initials: H
authors.lastname: Takano
authors.forename: H
authors.initials: H
authors.lastname: Tanimura
authors.forename: M
authors.initials: M
authors.lastname: Miyazaki
authors.forename: K
authors.initials: K
authors.lastname: Matsuo
authors.forename: K
authors.initials: K
authors.lastname: Hidaka
authors.forename: M
authors.initials: M
authors.lastname: Kuwano