Open AccessAdseverin: A novel cisplatin‐resistant marker in the human bladder cancer cell line HT1376 identified by quantitative proteomic analysis
Author(s) -
Miura Noriyoshi,
Takemori Nobuaki,
Kikugawa Tadahiko,
Tanji Nozomu,
Higashiyama Shigeki,
Yokoyama Masayoshi
Publication year - 2012
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1016/j.molonc.2011.12.002
Subject(s) - cisplatin , apoptosis , bladder cancer , downregulation and upregulation , gene knockdown , cancer cell , cell culture , mitochondrion , chemistry , cancer research , programmed cell death , biology , cancer , microbiology and biotechnology , biochemistry , gene , chemotherapy , genetics
Cisplatin is currently the most effective antitumor agent available against bladder cancer. However, a majority of patients eventually relapse with cisplatin‐resistant disease. Chemoresistance thus remains a major obstacle in bladder cancer therapy. To clarify the molecular mechanisms underlying cisplatin resistance in bladder cancer, we established a cisplatin‐resistant subline from the human bladder cancer cell line HT1376 (HT1376‐CisR), and conducted large‐scale analyses of the expressed proteins using two‐dimensional (2D) gel electrophoresis coupled with mass spectrometry (MS). Comparative proteomic analysis of HT1376 and HT1376‐CisR cells revealed 36 differentially expressed proteins, wherein 21 proteins were upregulated and 15 were downregulated in HT1376‐CisR cells. Among the differentially regulated proteins, adseverin (SCIN), a calcium‐dependent actin‐binding protein, was overexpressed (4‐fold upregulation) in HT1376‐CisR, with the increase being more prominent in the mitochondrial fraction than in the cytosol fraction. SCIN mRNA knockdown significantly reduced cell proliferation with mitochondria‐mediated apoptosis in HT1376‐CisR cells. Immunoprecipitation analysis revealed voltage‐dependent anion channels (VDACs) to be bound to SCIN in the mitochondrial fraction. Our results suggest that the VDAC‐SCIN interaction may inhibit mitochondria‐mediated apoptosis in cisplatin‐resistant cells. Targeting the VDAC‐SCIN interaction may offer a new therapeutic strategy for cisplatin‐resistant bladder cancer.