title: PKC α regulates netrin-1/UNC5B-mediated survival pathway in bladder cancer.
abstract: BACKGROUND
  Netrin-1 and its receptor UNC5B play important roles in angiogenesis, embryonic development, cancer and inflammation. However, their expression patttern and biological roles in bladder cancer have not been well characterized. The present study aims to investigating the clinical significance of PKC α, netrin-1 and UNC5B in bladder cancer as well as their association with malignant biological behavior of cancer cells.
  
  
  METHODS
  Netrin-1 and UNC5B expression was examined in 120 bladder cancer specimens using immunohistochemistry and in 40 fresh cancer tissues by western blot. Immunofluorescence was performed in cancer cell lines. PKC α agonist PMA and PKC siRNA was employed in bladder cancer cells. CCK-8, wound healing assays and flow cytometry analysis were used to examine cell proliferation, migration and cell cycle, respectively.
  
  
  RESULTS
  Netrin-1 expression was positively correlated with histological grade, T stage, metastasis and poor prognosis in bladder cancer tissues. Immunofluorescence showed elevated netrin-1 and decreased UNC5B expression in bladder cancer cells compared with normal bladder cell line. Furthermore, cell proliferation, migration and cell cycle progression were promoted with PMA treatment while inhibited by calphostin C. In addition, PMA treatment could induce while calphostin C reduce netrin-1 expression in bladder cancer cells.
  
  
  CONCLUSIONS
  The present study identified netrin-1/UNC5B, which could be regulated by PKC signaling, was important mediators of bladder cancer progression.
authors: Jiao
authors: J
authors: Liu
authors: Department of Urology, the First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, China. syliujiao@sohu.com.
authors: Chui-ze
authors: CZ
authors: Kong
authors: Da-xin
authors: DX
authors: Gong
authors: Zhe
authors: Z
authors: Zhang
authors: Yu-yan
authors: YY
authors: Zhu
mesh_terms: D000368:Aged; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000096:biosynthesis*; D000075386:Netrin Receptors; D000075388:Netrin-1; D051571:Protein Kinase C-alpha / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000096:biosynthesis*; D015398:Signal Transduction / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis*; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: C000617351:NTN1 protein, human; D009414:Nerve Growth Factors; D000075386:Netrin Receptors; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins; C532445:UNC5B protein, human; D000075388:Netrin-1; D051571:Protein Kinase C-alpha