The transmembrane protease serine (TMPRSS3/TADG-12) D variant: a potential candidate for diagnosis and therapeutic intervention in ovarian cancer.
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.
Sawasaki
Takashi
T
Department of Obstetrics and Gynecology, University of Arkansas for Medical Sciences, Little Rock, AR 72205-7199, USA.
Shigemasa
Kazushi
K
Gu
Lijun
L
Beard
John B
JB
O'Brien
Timothy J
TJ
D002288:Adenocarcinoma, Mucinous / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D000236:Adenoma / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D000595:Amino Acid Sequence; D002277:Carcinoma / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D002471:Cell Transformation, Neoplastic; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics*; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D012697:Serine Endopeptidases / Q000096:biosynthesis* / Q000235:genetics*
D008565:Membrane Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012697:Serine Endopeptidases; C417724:TADG-12 serine protease; C409042:TMPRSS3 protein, human