title: Up-regulation of Bfl-1/A1 via NF-kappaB activation in cisplatin-resistant human bladder cancer cell line.
abstract: The potent anti-cancer agent cis-diamminedichloroplatinum (II) (cisplatin) is currently used for treating bladder cancer. However, clinical use of this drug for long periods is often limited because of the appearance of cisplatin-resistant bladder tumor cells. We employed the method of a differential display reverse transcriptase polymerase chain reaction to identify the differentially expressed genes in the parental human bladder cancer cell line, T24 and three cisplatin-resistant cell lines. We report here that cisplatin-resistant cell lines overexpress Bcl-2 family protein Bcl-2-related gene expressed in fetal liver (Bfl-1)/A1 as compared with their parental cell. Cisplatin and gamma-irradiation induced expression of Bfl-1/A1 in T24R2 cells but not in T24 cells. Among Bcl-2 family members, Bfl-1/A1 showed the most significant alteration of the expression level in resistant cells. The nuclear translocation of nuclear factor-kappaB (NF-kappaB) by cisplatin and gamma-irradiation selectively occurred in T24R2 cells. Mitochondrial depolarization and cell death by cisplatin were also prevented in T24R2 cells. Moreover, Bfl-1/A1 inhibited cisplatin- and TNF-alpha-induced apoptosis in BOSC23 cells. Our findings suggest that the induction of Bfl-1/A1 by NF-kappaB may be important in controlling resistance to cisplatin responses in bladder tumor cells.
authors.affiliation: Laboratory of Cell Biology, Korea Research Institute of Bioscience and Biotechnology, P.O. Box 115, Yuseong, Daejeon 305-600, South Korea.
authors.forename: Jin Koo
authors.initials: JK
authors.lastname: Kim
authors.forename: Kwang Dong
authors.initials: KD
authors.lastname: Kim
authors.forename: Eunsik
authors.initials: E
authors.lastname: Lee
authors.forename: Jong-Seok
authors.initials: JS
authors.lastname: Lim
authors.forename: Hee-Jun
authors.initials: HJ
authors.lastname: Cho
authors.forename: Hyun Kyung
authors.initials: HK
authors.lastname: Yoon
authors.forename: Mi-Young
authors.initials: MY
authors.lastname: Cho
authors.forename: Kyoung-Eun
authors.initials: KE
authors.lastname: Baek
authors.forename: Yuk Pheel
authors.initials: YP
authors.lastname: Park
authors.forename: Sang-Gi
authors.initials: SG
authors.lastname: Paik
authors.forename: Yong-Kyung
authors.initials: YK
authors.lastname: Choe
authors.forename: Hee Gu
authors.initials: HG
authors.lastname: Lee
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D020869:Gene Expression Profiling; D006801:Humans; D015778:Minor Histocompatibility Antigens; D016328:NF-kappa B / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology*
chemical_list: D000970:Antineoplastic Agents; C096816:BCL2-related protein A1; D015778:Minor Histocompatibility Antigens; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D002945:Cisplatin