Heterogeneity of Cellular Proliferation within Transitional Cell Carcinoma: Correlation of Protein Kinase C /I Expression and Activity

Vesa Aaltonen ^1*, Jussi Koivunen ¹, Matti Laato ¹ and Juha Peltonen ¹

¹ Departments of Anatomy and Cell Biology (VA,JK,JP) and Dermatology (JP), University of Oulu, Oulu, Finland; Departments of Anatomy (JP), Dermatology (JP), Surgery (ML), and Medical Biochemistry (ML), University of Turku, Turku, Finland; and Department of Internal Medicine, Kainuu Central Hospital, Kajaani, Finland (JK)

^* To whom correspondence should be addressed. E-mail: vesaal{at}utu.fi.

Submitted on September 12, 2005
Accepted on 18 February 2006

	Abstract

A total of 18 histological samples containing both transitional cell carcinoma (TCC) and normal urothelial epithelium were analyzed for PKC and I expression, and for their phosphorylated substrates. The results showed an increased expression of PKC in 13 out of 18 samples and I in 11 out of 18 TCC samples when compared with normal urothelium. In addition, 11 out of 18 of the TCC tumors displayed heterogeneous expression of the PKC isoenzymes, with different levels of immunosignal in different areas of the tumor. Within the same sample, areas of highest PKC isoenzyme expression also showed highest classical PKC activity, as estimated by immunodetection of phosphorylated forms of PKC substrates. The areas of highest expression of PKC and/or I isoenzymes showed also highest number of cells positive for Ki67, an indicator of proliferation. Immunofluorescence and Western blotting demonstrated that in cultured TCC cells, PKC was located in the cytoplasm whereas PKCI was located primarily in nucleus as a 65 kDa fragment and in cytoplasm as a full size 79 kDa protein. Our results indicate that increased expression of PKC and I leads to increased total classical PKC kinase activity and suggest that increased activity of the isoenzymes play a role in accelerated growth of TCC. Furthermore, these results suggest that even in carcinoma tissue, the PKC expression and activity are under strict control.

Key Words: protein kinase C, alpha, betaI, bladder, carcinoma, expression, proliferation

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