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Overexpression of Testisin, a Serine Protease Expressed by Testicular Germ Cells, in Expithelial Ovarian Tumor Cells

Department of Obstetrics and Gynecology, Hiroshima University School of Medicine, Hiroshima, Japan; Department of Obstetrics and Gynecology, Asada General Hospital, Marugame, Japan; Departments of Obstetrics and Gynecology and Biochemistry and molecular Biology, University of Arkansas for Medical Sciences, Little Rock, Arkansas kaz{at}mcai.med.hiroshima-u.ac.jp

Lowell J. Underwood, PhD

John Beard, BS

Hirotoshi Tanimoto, MD

Koso Ohama, MD

Tim H. Parmley, MD

Timothy J. O'Brien, PhD

Department of Obstetrics and Gynecology, Hiroshima University School of Medicine, Hiroshima, Japan; Department of Obstetrics and Gynecology, Asada General Hospital, Marugame, Japan; Departments of Obstetrics and Gynecology and Biochemistry and molecular Biology, University of Arkansas for Medical Sciences, Little Rock, Arkansas

Objective: In a continued effort to identify and characterized secreted proteases that are overexpressed in ovarian carcinomas, we discovered the testisin protease as such a candidate. When this discovery was originally made, no data existed in the literature or in the GenBank database that identified such a gene. Our main objective was to determine whether this gene was overexpressed exclusively in ovarian tumor tissues compared with normal ovary and whether it was expressed in any other normal tissues.

Methods: mRNA was isolated and cDNA was prepared from 34 ovarian tumors (four adenomas, three low malignant potential tumors, and 37 carcinomas) and seven normal ovaries. The testisin mRNA expression level relative to internal control, ß-tubulin, was determined by Northern blot analysis and semiquantitative polymerase chain reaction (PCR).

Results: Northern blot hybridization showed that the testisin transcript was abundant in ovarian carcinoma but was not detected in normal ovary. On examination of Northern blots from normal fetal and adult tissues, only adult testis showed abundant transcripts of testisin. Semiquantitative PCR examination showed that the testisin mRNA levels in ovarian tumors of low malignant potential and in ovarian carcinomas were significantly higher than in normal ovaries (P < .01). Testisin mRNA level in ovarian carcinomas was also significantly higher than in ovarian adenomas (P < .05). Testisin overexpression rates in advanced stage (stage 2 or 3) diseases were significantly higher than that in early stage disease (stage 1) in ovarian carcinoma samples (P < .05).

Conclusions: The induction of the testisin transcript might contribute to the development, progression, and invasive or metastatic capacity of ovarian carcinomas.

Key Words: Testisin • serine prottease • mRNA • overexpression • ovarian tumor

Journal of the Society for Gynecologic Investigation, Vol. 7, No. 6, 358-362 (2000)
DOI: 10.1177/107155760000700608


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