Protein C inhibitor in the human endometrium

Protein C Inhibitor (PCI), also known as Plasminogen Activator Inhibitor-3, is a serine protease inhibitor (serpin) that regulates a variety of proteases. PCI is mainly present in the coagulation cascade; however it is also known to inhibit proteases involved in tumor invasion and metastasis. The endometrium is a hormonally responsive exocrine gland that is a common site of tumor formation in women. Tumors of the endometrium predominately arise in the glandular epithelial cells of the tissue that invade the underlying endometrial stroma during progression. Using i m muno hist o chemistry, we detected PCI antigen in both normal and malignant endometrium in vivo. The immunoreactivity appeared weaker in the normal tissue specimens when compared to the carcinomas tested. PCI was localized to the glandular epithelial cells along with diffuse staining in the stromal compartment. This result differs from immunostaining for two other coagulation serpins, Antithrombin HI and Heparin Cofactor II, which are not present outside the vasculature of normal or malignant endometrium. In vitro, endometrial carcinoma cell lines produce both PCI mRNA and protein. The PCI gene contains an estrogen responsive element in its promoter region, however PCI does not appear to be transcriptionally regulated by estrogen in either Ishikawa or HEC-lB endometrial cancer cell lines. PCI may play a role in regulating the proteolytic cascade that facilitates the destruction of normal tissue architecture in the human endometrium during the metastatic process.

Duke Scholars

Author Maureane Hoffman Pathology