Overexpression of kallikrein 10 in epithelial ovarian carcinomas.
OBJECTIVE
We wanted to identify genes up-regulated in ovarian tumors that might serve as early markers for ovarian cancer. One promising focus is the family of genes that encode secreted proteases, which play essential roles in tumor invasion and metastasis. Kallikrein 10 (KLK10) is a member of the kallikrein family of serine proteases which include 15 proteins, including the prostate-specific antigen (PSA), also known as hK3. We investigated whether KLK10 and its related protein, hK10, might serve as equally accurate markers for ovarian carcinoma.


METHODS
Transcriptional profiling was performed using RNA isolated from normal ovarian epithelium, ovarian cancer cell lines, and primary ovarian tumors. Microarray data were confirmed by Northern blot analysis of 66 ovarian tumor samples and 6 ovarian cancer cell lines. In situ hybridization and Western blot analysis confirmed the Northern blot findings.


RESULTS
KLK10 was more highly expressed by primary ovarian tumors than by NOE. Thirty-two of 35 primary serous ovarian carcinoma samples (91.4%) expressed higher levels of KLK10 than NOE did. Eleven of 15 nonserous epithelial ovarian carcinoma samples (73.3%) and 8 of 11 primary peritoneal carcinoma samples (72.7%) also expressed KLK10. Overall, 84.8% of all epithelial ovarian and peritoneal carcinoma tumor samples showed elevated expression of KLK10. Similarly, Western blot analysis demonstrated that levels of the KLK10-related protein, designated hK10, are elevated in primary ovarian tissue lysates, but the protein is undetectable in immortalized ovarian epithelium. Finally, in situ hybridization established that KLK10 mRNA is much more highly expressed by tumor tissue than by normal epithelium and stromal tissues.


CONCLUSIONS
Our data support recent immunoassay findings of elevated levels of hK10 in the tumor tissue and serum of ovarian cancer patients. Thus, it is likely that KLK10 and other kallikreins will serve as useful diagnostic and prognostic markers in patients with ovarian carcinoma.
Shvartsman
Hyun S
HS
Department of Gynecologic Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA. hshvarts@mdanderson.org
Lu
Karen H
KH
Lee
John
J
Lillie
Jim
J
Deavers
Michael T
MT
Clifford
Stephanie
S
Wolf
Judith K
JK
Mills
Gordon B
GB
Bast
Robert C
RC
Gershenson
David M
DM
Schmandt
Rosemarie
R
D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D015152:Blotting, Northern; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D017403:In Situ Hybridization; D007610:Kallikreins / Q000096:biosynthesis* / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; C100936:KLK10 protein, human; D007610:Kallikreins