Previous studies indicated that a new member of the human kallikrein (KLK)
gene family, KLK4, was expressed in prostate, breast, and endometrial carci
noma cell lines and may have potential as a tumor marker. The aim of this s
tudy was to examine the expression of KLK4 in the normal ovary and ovarian
tumors of different histology, stage, and differentiation and to determine
its association with ovarian tumor progression. Using reverse transcription
-PCR, Southern blot, and densitometry analyses, we found the level of KLK4
expression was higher in late stage serous (SER) epithelial-derived ovarian
carcinomas than in normal ovaries, mucinous epithelial tumors, and granulo
sa cell tumors. KLK4 was highly expressed in all of the SER ovarian carcino
ma cell lines (eight of eight), SER epithelial carcinomas (11 of 11), and t
wo adenomas, whereas it was expressed at a lower level (or not at all) in n
ormal ovaries (four of six), mucinous epithelial tumors (three of four), en
dometrioid carcinomas (four of five), clear cell carcinomas (two of three),
or granulosa cell tumors (three of six). Of particular interest, KLK4 mRNA
variants were detected in SER ovarian carcinoma cell lines and primary cul
tured ovarian tumor cells, but they were not present in normal ovaries. In
situ hybridization analysis showed that KLK4 mRNA transcripts are localized
to adenocarcinoma cells of ovarian tumor tissues. Similarly, immunohistoch
emical staining of ovarian carcinoma sections showed immunoreactivity to KL
K4 protein product (hK4) antipeptide antibodies. In addition, intracellular
hK4 levels, as detected on Western blot analysis, were induced by 100 nM e
strogen treatment of the estrogen receptor positive ovarian carcinoma cell
line OVCAR-3, >8-24 h. Our results show that the level of KLK4 expression a
nd expression of KLK4 mRNA variants are associated with progression of ovar
ian cancer, particularly late stage SER adenocarcinomas. Moreover, hK4 may
be a candidate marker for the diagnosis and/or monitoring of ovarian epithe
lial carcinomas.