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Testisin, a new human serine proteinase expressed by premeiotic testicular germ cells and lost in testicular germ cell tumors

Hooper, John D., Nicol, David L. , Dickinson, Joanne L., Eyre, Helen J., Scarman, Anthony L., Normyle, John F., Stuttgen, Melanie A., Douglas, Meaghan L. , Lakoski-Loveland, Kate A., Sutherland, Grant R., & Antalis, Toni M. (1999) Testisin, a new human serine proteinase expressed by premeiotic testicular germ cells and lost in testicular germ cell tumors. Cancer Research, 59(13), pp. 3199-3205.

Abstract

We have cloned and characterized a cDNA encoding a new human serine proteinase, testisin, that is abundantly expressed only in the testis and is lost in testicular tumors. The testisin cDNA was identified by homology cloning using degenerate primers directed at conserved sequence motifs within the catalytic regions of serine proteinases. It is 1073 nucleotides long, including 942 nucleotides of open reading frame and a 113-nucleotide 3* untranslated sequence. Northern and dot blot analyses of RNA from a range of normal human tissues revealed a 1.4-kb mRNA species that was present only in testis, which was not detected in eight of eight testicular tumors. Testisin cDNA is predicted to encode a protein of 314 amino acids, which consists of a 19-amino acid (aa) signal peptide, a 22-aa proregion, and a 273-aa catalytic domain, including a unique 17-aa COOH-terminal hydrophobic extension that is predicted to function as a membrane anchor. The deduced amino acid sequence of testisin shows 44% identity to prostasin and contains features that are typical of serine proteinases with trypsin-like substrate specificity. Antipeptide antibodies directed against the testisin polypeptide detected an immunoreactive testisin protein of Mr 35,000–39,000 in cell lysates from COS-7 cells that were transiently transfected with testisin cDNA. Immunostaining of normal testicular tissue showed that testisin was expressed in the cytoplasm and on the plasma membrane of premeiotic germ cells. No staining was detected in eight of eight germ cell-derived testicular tumors. In addition, the testisin gene was localized by fluorescence in situ hybridization to the short arm of human chromosome 16 (16p13.3), a region that has been associated with allellic imbalance and loss of heterozygosity in sporadic testicular tumors. These findings demonstrate a new cell surface serine proteinase, loss of which may have a direct or indirect role in the progression of testicular tumors of germ cell origin.

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ID Code: 8707
Item Type: Journal Article
Additional Information: Self-archiving of the author-version is not yet supported by this publisher. For more information, please refer to the journal’s website (see hypertext link) or contact the author. jd.hooper@qut.edu.au
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ISSN: 0008-5472
Divisions: Past > QUT Faculties & Divisions > Faculty of Science and Technology
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 1999 American Association for Cancer Research
Deposited On: 19 Jul 2007
Last Modified: 11 Aug 2011 02:31

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