BACKGROUND. Molecules that are highly expressed by human prostate cancers m
ay serve as therapeutically relevant targets or tumor markers. Tyrosine kin
ases are frequently overexpressed in metastatic tumor cells and this prompt
ed us to screen for tyrosine kinases that are overexpressed in prostate can
cer cells.
METHODS. Expression levels of the EphA2 receptor tyrosine kinase were deter
mined by Western blot analysis in canine and human prostate cancer cell lin
es and in immortalized and transformed variants of 267B1 prostatic epitheli
al cells. EphA2 levels in benign human prostate and prostate cancers were a
lso determined in formalin-fixed, paraffin-embedded tissues using immunohis
tochemical staining.
RESULTS. Metastatic prostate cancer cells overexpressed EphA2 by 10-100 fol
d as compared with non-invasive prostatic epithelial cells. EphA2 immunorea
ctivity in vivo was also significantly greater in human prostate cancers as
compared with benign prostate epithelium.
CONCLUSIONS. The EphA2 receptor tyrosine kinase is differentially expressed
in human and canine prostate cancer cell lines and overexpressed in human
prostate cancers as compared with benign prostate tissues. Metastasis-deriv
ed canine prostate carcinoma cell lines overexpress EphA2 and may provide p
re-clinical models to further evaluate the role of EphA2 in prostate carcin
ogenesis. Further investigations are needed to determine the utility of Eph
A2! as a tumor marker and a novel target in human prostate cancer. (C) 1999
Wiley-Liss, Inc.