title: Down-regulation of UNC5D in bladder cancer: UNC5D as a possible mediator of cisplatin induced apoptosis in bladder cancer cells.
abstract: OBJECTIVE
  Identifying potential targets would improve therapeutic planning and disease management. Therefore, we investigated whether the novel identified dependence receptor UNC5D acts as a tumor suppressor in bladder malignancies.
  
  
  METHODS
  We assessed the UNC5D level in a panel of 15 primary bladder carcinomas and 6 cell lines using real-time reverse transcriptase-polymerase chain reaction and Western blot. MTT assay, TUNEL staining, colony formation assay and Western blot were done in cells untransfected and transfected with UNC5D vector, siUNC5D or siDAPK.
  
  
  RESULTS
  UNC5D was dramatically down-regulated in bladder cancer tissue samples and malignant cell lines. Restoration of UNC5D expression in bladder cancer cells lacking endogenous UNC5D expression suppressed cell proliferation and survival. Cisplatin treatment significantly induced UNC5D expression and DAPK dephosphorylation while UNC5D knockdown decreased bladder cancer cell sensitivity to cisplatin. DAPK silencing significantly inhibited the effect of UNC5D on apoptosis induced by cisplatin.
  
  
  CONCLUSIONS
  Our study suggests that UNC5D may have important roles as a novel suppressor in bladder cancer via the UNC5D/DAPK pathway.
authors: Department of Urology, First Affiliated Hospital of China Medical University, Shenyang, People's Republic of China; Institute of Urology, China Medical University, Shenyang, People's Republic of China. Electronic address: zhyy88@hotmail.com.
authors: Yuyan
authors: Y
authors: Zhu
authors: Department of Reproductive Biology and Transgenic Animals, China Medical University, Shenyang, People's Republic of China.
authors: Meng
authors: M
authors: Yu
authors: Department of Urology, First Affiliated Hospital of China Medical University, Shenyang, People's Republic of China; Institute of Urology, China Medical University, Shenyang, People's Republic of China.
authors: Yifu
authors: Y
authors: Chen
authors: Department of Urology, First Affiliated Hospital of China Medical University, Shenyang, People's Republic of China; Institute of Urology, China Medical University, Shenyang, People's Republic of China.
authors: Yixia
authors: Y
authors: Wang
authors: Department of Urology, First Affiliated Hospital of China Medical University, Shenyang, People's Republic of China; Institute of Urology, China Medical University, Shenyang, People's Republic of China.
authors: Junyong
authors: J
authors: Wang
authors: Department of Urology, First Affiliated Hospital of China Medical University, Shenyang, People's Republic of China; Institute of Urology, China Medical University, Shenyang, People's Republic of China.
authors: Chunming
authors: C
authors: Yang
authors: Department of Urology, First Affiliated Hospital of China Medical University, Shenyang, People's Republic of China; Institute of Urology, China Medical University, Shenyang, People's Republic of China.
authors: Jianbin
authors: J
authors: Bi
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology / Q000627:therapeutic use*; D015536:Down-Regulation; D005260:Female; D006801:Humans; D008297:Male; D011956:Receptors, Cell Surface / Q000502:physiology*; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000473:pathology*
chemical_list: D000970:Antineoplastic Agents; D011956:Receptors, Cell Surface; C529231:UNC5D protein, human; D002945:Cisplatin
keywords: UNC5H4 protein; cisplatin; death-associated protein kinases; human; urinary bladder; urinary bladder neoplasms