Role of protein kinase C-alpha in superficial bladder carcinoma recurrence

To investigate the role of protein kinase C-alpha (PKCalpha) in the recurrence of superficial bladder carcinoma.

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.

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).

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.