The transmembrane protease serine (TMPRSS3/TADG-12) D variant: a potential candidate for diagnosis and therapeutic intervention in ovarian cancer

Tumour Biol. May-Jun 2004;25(3):141-8. doi: 10.1159/000079146.

Abstract

The purpose of this study was to examine the expression of splice variants of the TADG-12 (TMPRSS3) gene in normal ovarian epithelial tissue and ovarian carcinoma and further to associate the expression of TADG-12 variant with clinicopathologic characteristics if such an association exists. TADG-12D variant expression was examined by semiquantitative PCR in 50 ovarian tumors [41 adenocarcinomas, 3 low malignant potential (LMP) tumors, and 6 adenomas] and 7 normal ovaries. In carcinomas as well as LMP tumors and adenomas, TADG-12D variant mRNA expression was significantly elevated compared to that in normal ovary samples. TADG-12 has several splice variants, one of which we originally identified and 3 others identified by Scott et al. [Nat Genet 2001;27:59-63]. We previously examined the expression of TADG-12V variant and here we confirm the overexpression of TADG-12D variant in ovarian carcinomas. Moreover, TADG-12D variant mRNA expression level in carcinomas was significantly elevated compared to that in adenomas and TADG-12D variant mRNA expression level in advanced clinical stage diseases was significantly higher than that in early stage diseases in ovarian carcinomas. With regard to histological type, TADG-12D variant mRNA expression level in mucinous adenocarcinomas was significantly higher than those in the other tissue subtypes. These features imply that TADG-12D variant expression may play an important role in ovarian cancer development and progression, and this variant may be useful both as a molecular target for therapy and/or a diagnostic marker.

MeSH terms

  • Adenocarcinoma, Mucinous / diagnosis
  • Adenocarcinoma, Mucinous / genetics*
  • Adenocarcinoma, Mucinous / therapy
  • Adenoma / diagnosis
  • Adenoma / genetics*
  • Adenoma / therapy
  • Amino Acid Sequence
  • Carcinoma / diagnosis
  • Carcinoma / genetics*
  • Carcinoma / therapy
  • Cell Transformation, Neoplastic
  • Female
  • Gene Expression Profiling*
  • Humans
  • Membrane Proteins / biosynthesis*
  • Membrane Proteins / genetics*
  • Molecular Sequence Data
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / genetics*
  • Ovarian Neoplasms / diagnosis
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / therapy
  • Polymerase Chain Reaction
  • RNA, Messenger / analysis
  • RNA, Messenger / biosynthesis
  • Serine Endopeptidases / biosynthesis*
  • Serine Endopeptidases / genetics*

Substances

  • Membrane Proteins
  • Neoplasm Proteins
  • RNA, Messenger
  • Serine Endopeptidases
  • TADG-12 serine protease
  • TMPRSS3 protein, human