Serine proteases serve many functions in normal biological processes. These functions are often usurped by
cancer cells to allow progression of
tumors by increasing the growth and metastatic potential of the
neoplasia. Here, we have used a polymerase chain reaction (PCR)-based strategy to clone
Tumor Associated Differentially-expressed Gene-12 (TADG-12), a new
serine protease from ovarian
carcinoma. This technique also revealed a variant splicing form of
TADG-12 that could lead to a truncated
protein product. Semi-quantitative PCR showed that
TADG-12 is overexpressed in 41 of 55
ovarian cancer specimens relative to normal expression, and the variant form, TADG-12V is found at increased levels in 8 of 22
carcinomas examined. Northern blot revealed three transcripts, the largest of which is approximately 2.4 kb. An ovarian
tumor cDNA library was screened, and the entire
cDNA of
TADG-12 has been identified. This sequence encodes a putative
protein of 454
amino acids which includes a potential transmembrane domain, an
LDL receptor-like domain, a
scavenger receptor cysteine-rich domain, and a
serine protease domain. These features imply that
TADG-12 will be at the cell surface, and it may be useful as a molecular target for
therapy or a diagnostic marker.