Up-regulation of Bfl-1/A1 via NF-kappaB activation in cisplatin-resistant human bladder cancer cell line.
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.
Kim
Jin Koo
JK
Laboratory of Cell Biology, Korea Research Institute of Bioscience and Biotechnology, P.O. Box 115, Yuseong, Daejeon 305-600, South Korea.
Kim
Kwang Dong
KD
Lee
Eunsik
E
Lim
Jong-Seok
JS
Cho
Hee-Jun
HJ
Yoon
Hyun Kyung
HK
Cho
Mi-Young
MY
Baek
Kyoung-Eun
KE
Park
Yuk Pheel
YP
Paik
Sang-Gi
SG
Choe
Yong-Kyung
YK
Lee
Hee Gu
HG
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*
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