Objective. The high temperature requirement factor A3 (HtrA3) is a
serine protease homologous to bacterial HtrA. Four human HtrAs have been identified. HtrA1 and HtrA3 share a high degree of domain organization and are downregulated in a number of
cancers, suggesting a widespread loss of these
proteases in
cancer. This study examined how extensively the HtrA (HtrA1-3)
proteins are downregulated in commonly used
cancer cell lines and primary ovarian
tumors.Methods. RT-PCR was applied to various
cancer cell lines (n=17) derived from the ovary, endometrium, testes, breast, prostate, and colon, and different subtypes of primary ovarian
tumors [granulosa cell tumors (n=19),
mucinous cystadenocarcinomas (n=6),
serous cystadenocarcinomas (n=8)] and normal ovary (n = 9). HtrA3
protein was localized by immunohistochemistry.Results. HtrA3 was extensively downregulated in the
cancer cell lines examined including the
granulosa cell tumor-derived cell lines. In primary ovarian
tumors, the HtrA3 was significantly lower in
serous cystadenocarcinoma and
granulosa cell tumors. In contrast, HtrA1 and HtrA2 were expressed in all samples with no significant differences between the control and
tumors. In normal postmenopausal ovary, HtrA3
protein was localized to lutenizing stromal cells and corpus albicans. In
serous cystadenocarcinoma, HtrA3
protein was absent in the papillae but detected in the mesenchymal
cyst wall.Conclusion. HtrA3 is more extensively downregulated than HtrA1-2 in
cancer cell lines. HtrA3, but not HtrA1 or HtrA2, was decreased in primary ovarian
serous cystadenocarcinoma and
granulosa cell tumors. This study provides evidence that HtrA3 may be the most relevant HtrA associated with ovarian
malignancy.