The novel serine protease tumor-associated differentially expressed gene-14 (KLK8/Neuropsin/Ovasin) is highly overexpressed in cervical cancer.
OBJECTIVE
Serine proteases are redundant enzymes implicated in the extracellular modulation required for tumor growth and invasion. Tumor-associated differentially expressed gene-14 (TADG-14) is a novel transmembrane serine protease recently reported by our group to be highly overexpressed in ovarian carcinomas. The goal of this study was to investigate the frequency of expression of the TADG-14 gene in human cervical tumors.


METHODS
TADG-14 expression was evaluated in 19 cervical cancer cell lines (11 primary and 8 established cell lines) as well as in 8 normal cervical keratinocyte cultures by reverse transcriptase polymerase chain reaction. In addition, to validate gene expression data at the protein level, TADG-14 expression was evaluated by immunohistochemistry on paraffin-embedded tissue from which all 11 primary tumor cell lines were established.


RESULTS
TADG-14 was found to be highly expressed in 82% (9/11) primary cervical cancer cell lines and in 87% (7/8) established cervical cancer cell lines by reverse transcriptase-polymerase chain reaction. Expression of TADG-14 by primary squamous cervical tumors was 100% (6/6), whereas 60% (3/5) of primary adenocarcinomas expressed TADG-14. In contrast, none of the normal cervical keratinocyte control cultures (n=4) or flash frozen normal cervical biopsy specimens (n=4) expressed TADG-14. Immunohistochemistry staining of paraffin-embedded cervical cancer specimens confirmed TADG-14 expression in tumor cells and its absence on normal cervical epithelial cells.


CONCLUSIONS
Cervical cancer expressed a high level of TADG-14, suggesting that this protease may play an important role in invasion and metastasis. Because TADG-14 appears only in abundance in tumor tissue and contains a secretion signal sequence, suggesting that TADG-14 is secreted, it may prove to be a useful diagnostic tool for the early detection of recurrent/persistent cervical cancer after standard treatment or as a novel molecular target for cervical cancer therapy.
Cané
Stefania
S
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Arkansas for Medical Sciences, Little Rock, AR 72205,USA.
Bignotti
Eliana
E
Bellone
Stefania
S
Palmieri
Michela
M
De las Casas
Luis
L
Roman
Juan J
JJ
Pecorelli
Sergio
S
Cannon
Martin J
MJ
O'brien
Timothy
T
Santin
Alessandro D
AD
D000230:Adenocarcinoma / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D002584:Cervix Uteri / Q000166:cytology / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D007610:Kallikreins / Q000235:genetics / Q000378:metabolism*; D015603:Keratinocytes / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D002583:Uterine Cervical Neoplasms / Q000378:metabolism*
C094799:KLK8 protein, human; D007610:Kallikreins