title: Role of protein kinase C-alpha in superficial bladder carcinoma recurrence.
abstract: OBJECTIVE
  To investigate the role of protein kinase C-alpha (PKCalpha) in the recurrence of superficial bladder carcinoma.
  
  
  METHODS
  Expression of PKCalpha was measured by Western blot analysis in 56 samples. A human RT-4 bladder cancer cell line stably expressing green fluorescent protein-PKCalpha (RT-4/PKCalpha) was established. The sensitivity of the RT-4/PKCalpha and parental cells to adriamycin (ADM) was determined by MTT assay. We also observed a change in the sensitivity of RT-4/PKCalpha to ADM under the conditions of PKCalpha upregulation and downregulation.
  
  
  RESULTS
  PKCalpha expression and the ratio of PKCalpha expression in the membrane to that in cytosol were greater in cancerous tissues than in normal tissues (P <0.05). With an increase in tumor grade, the level of PKCalpha expression increased significantly in the membrane (P <0.01) and decreased in cytosol (P <0.01). Patients with superficial bladder carcinoma with a greater membrane/cytosol ratio of PKCalpha had a shorter recurrence-free period than did those with lower levels after standard ADM treatment at 2 years of follow-up (P <0.05). In vitro transfection of PKCalpha increased resistance of RT-4 cells to ADM (P<0.01). Activation of PKCalpha also greatly promoted resistance (P <0.001), and inhibition of PKCalpha decreased resistance (P <0.01).
  
  
  CONCLUSIONS
  Our results have shown the correlation of PKCalpha overexpression/activation in superficial bladder carcinoma with the effect of ADM on tumor recurrence. PKCalpha may play an important role, not only in tumor differentiation, but also in intrinsic resistance to chemotherapy drugs by activation of the PKC pathway.
authors.affiliation: Department of Urology, No. 1 Hospital, China Medical University, Shenyang, People's Republic of China. urokong@hotmail.com
authors.forename: Chuize
authors.initials: C
authors.lastname: Kong
authors.forename: Yuyan
authors.initials: Y
authors.lastname: Zhu
authors.forename: Donghui
authors.initials: D
authors.lastname: Liu
authors.forename: Meng
authors.initials: M
authors.lastname: Yu
authors.forename: Shi
authors.initials: S
authors.lastname: Li
authors.forename: Zeliang
authors.initials: Z
authors.lastname: Li
authors.forename: Zhixi
authors.initials: Z
authors.lastname: Sun
authors.forename: Gefei
authors.initials: G
authors.lastname: Liu
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D002295:Carcinoma, Transitional Cell / Q000201:enzymology*; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism*; D051571:Protein Kinase C-alpha / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000201:enzymology*
chemical_list: D051571:Protein Kinase C-alpha