Human kallikrein 4 (KLK4) is highly expressed in serous ovarian carcinomas

Citation
Y. Dong et al., Human kallikrein 4 (KLK4) is highly expressed in serous ovarian carcinomas, CLIN CANC R, 7(8), 2001, pp. 2363-2371
Citations number
33
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Oncology
Journal title
CLINICAL CANCER RESEARCH
ISSN journal
1078-0432 → ACNP
Volume
7
Issue
8
Year of publication
2001
Pages
2363 - 2371
Database
ISI
SICI code
1078-0432(200108)7:8<2363:HK4(IH>2.0.ZU;2-M
Abstract
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.