Protein kinase c isoenzyme patterns characteristically modulated in early prostate cancer

Expression of protein kinase C (PKC) isoenzymes -alpha, -beta, -delta, -eps ilon, -gamma, -iota, -lambda, -mu, -theta, and -zeta, and of their common r eceptor for activated C-kinase (RACK)-1, was determined immunohistochemical ly using specific antibodies in formalin-fixed and paraffin-embedded specim ens of early prostatic adenocarcinomas (n = 23) obtained at radical prostat ectomy. Expression of each isoenzyme by malignant tissues was compared with nonneoplastic prostate tissues removed at radical cystectomy (n = 10), The most significant findings were decreased PRC-beta expression in early neop lasia when compared to benign epithelium (P < 0.0001), together with a reci procal increase in expression of PKC-epsilon (P < 0.0001). Detectable level s of PKC-alpha and PKC-zeta were also significantly increased in the cancer s (P = 0.045 and P = 0.015 respectively but did not correlate with either P KC-beta or PKC-epsilon for individual cases. Alterations in the levels of t he four PRC isoenzymes occurred specifically and consistently during the ge nesis and progression of human prostate cancer. PKC-delta, -gamma, and -the ta were not expressed in the epithelium of either the benign prostates or t he cancers. Levels of expression for PKC-lambda, -iota, -mu, and RACK-1 wer e not significantly different between the benign and malignant groups. Alth ough changes in PKC isoenzyme expression may assist in explaining an altere d balance between proliferation and apoptosis, it is likely that changes in activity or concentrations of these isoenzymes exert important modulating influences on particular pathways regulating cellular homeostasis, The find ings of this study raise an exciting possibility of novel therapeutic inter vention to regulate homeostatic mechanisms controlling proliferation and/or apoptosis, including expression of the p170 drug-resistance glycoprotein, intracellular Ca2+ concentrations, and enhanced cellular mobility resulting in the metastatic dissemination of human prostate cancer cells. Attenuatio n of PKC-beta expression is currently being assessed as a reliable objectiv e adjunct to morphological appearance for the diagnosis of early progressiv e neoplasia in human prostatic tissues.