Abstract
Objectives To investigate the role of protein kinase C-alpha (PKCα) in the recurrence of superficial bladder carcinoma. Methods Expression of PKCα was measured by Western blot analysis in 56 samples. A human RT-4 bladder cancer cell line stably expressing green fluorescent protein-PKCα (RT-4/PKCα) was established. The sensitivity of the RT-4/PKCα and parental cells to adriamycin (ADM) was determined by MTT assay. We also observed a change in the sensitivity of RT-4/PKCα to ADM under the conditions of PKCα upregulation and downregulation. Results PKCα expression and the ratio of PKCα 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 PKCα 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 PKCα 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 PKCα increased resistance of RT-4 cells to ADM ( P<0.01). Activation of PKCα also greatly promoted resistance ( P <0.001), and inhibition of PKCα decreased resistance ( P <0.01). Conclusions Our results have shown the correlation of PKCα overexpression/activation in superficial bladder carcinoma with the effect of ADM on tumor recurrence. PKCα may play an important role, not only in tumor differentiation, but also in intrinsic resistance to chemotherapy drugs by activation of the PKC pathway.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call