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From the Departments of Surgery*
and
Pathology,
The University of Liverpool, and
the Department of Urology,
The Royal
Liverpool University Hospital, Liverpool, United Kingdom
Expression of protein kinase C (PKC) isoenzymes -
,
-ß, -
, -
, -
, -
,
-
, -µ, -
, and -
, and of
their common receptor for activated C-kinase (RACK)-1, was
determined immunohistochemically using specific antibodies in
formalin-fixed and paraffin-embedded specimens of early prostatic
adenocarcinomas (n = 23) obtained at radical
prostatectomy. 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 PKC-ß expression in early neoplasia when compared to
benign epithelium (P < 0.0001), together
with a reciprocal increase in expression of PKC-
(P < 0.0001). Detectable levels of PKC- and
PKC- were also significantly increased in the cancers
(P = 0.045 and P = 0.015
respectively) but did not correlate with either PKC-ß or PKC- for
individual cases. Alterations in the levels of the four PKC isoenzymes
occurred specifically and consistently during the genesis and
progression of human prostate cancer. PKC-, -,
and - were not expressed in the epithelium of either the benign
prostates or the cancers. Levels of expression for PKC-,
-, -µ, and RACK-1 were not significantly different
between the benign and malignant groups. Although changes in PKC
isoenzyme expression may assist in explaining an altered 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 findings of this study raise an exciting possibility
of novel therapeutic intervention 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. Attenuation of PKC-ß expression is currently
being assessed as a reliable objective adjunct to morphological
appearance for the diagnosis of early progressive neoplasia in human
prostatic tissues.
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