Protein Kinase C-alpha is Expressed and Activated During the Development of Renal Cell Carcinoma

Abstract

To evaluate protein kinase C-alpha (PKCalpha) expression in human renal cell carcinoma (RCC) tissues and cell lines, and its clinical significance. Expression of PKCalpha was analyzed by Western blot in 90 clinical specimens. The expression of PKCalpha in the cytoplasm or plasma membrane was correlated to clinical stage and grade to assess for potential relationships. A human renal cell carcinoma (RCC) cell line (786-O/PKCalpha) was generated with stable expression of a fusion protein of green fluorescent protein (GFP) and PKCalpha, to facilitate analysis of in situ compartmentalization of PKCalpha during activation. PKCalpha expression and the ratio of PKCalpha expression in the membrane (M) to that in cytosol (C) were greater in cancerous tissues than in normal tissues (P <.05). With an increase in tumor grade and stage, the level of PKCalpha increased significantly in membrane (P <.01) and decreased in cytosol (P <.01). Consistently, there was an increase of M/C with increasing malignancy of tumor. As expected, the translocation of PKCalpha between plasma membrane and cytosol could be observed in 786-O renal carcinoma cells with the treatment of PKCalpha agonist or inhibitor. We demonstrated differential PKCalpha expression in RCC tissues, indicating that abnormal PKCalpha activation may contribute to the development of RCC.