Protein C inhibitor (PCI), a member of the serine protease inhibitor family, is produced in various human tissues, including the liver, kidney and testis. In addition to inhibiting the anticoagulant protein C pathway, PCI also inhibits urinary plasminogen activator (uPA), which is a well-known mediator of tumor cell invasion. In the present study, to clarify the biologic significance of PCI in the kidney, we compared the expression of PCI between human renal cell carcinoma (RCC) tissue and nontumor kidney tissue. The PCI antigen level in RCC tissue was found to be significantly lower than in nontumor kidney tissue, and expression of PCI mRNA was detected in normal renal proximal tubular epithelial cells (RPTEC), but not in RCC or in an RCC cell line (Caki-1 cells). Key words: protein C inhibitor; urinary plasminogen activator; renal cell carcinoma; tumor invasionProtein C inhibitor (PCI) was originally identified as an inhibitor of the anticoagulant protease, activated protein C, 1 and was subsequently found to inhibit other proteases involved in blood coagulation and fibrinolysis, such as thrombin, 2 thrombin-thrombomodulin complex, 3 factor Xa, 2 factor XIa, 4 plasma kallikrein 4 and urinary plasminogen activator (uPA). 5 Human plasma PCI is believed to be produced mainly by the liver, 6 but is also synthesized in the kidneys and the reproductive organs, including the testis, seminal vesicles and ovary. 7,8 Thus, besides its function in the regulation of blood coagulation, PCI may also play a role in the regulation of reproduction. Recently, Uhrin et al. 9 reported that PCI knockout male mice are apparently healthy but infertile, and that this infertility is caused by abnormal spermatogenesis induced by destruction of the Sertoli cell barrier. In the kidneys, PCI is mainly synthesized by proximal tubular epithelial cells, 10 and most urinary PCI is present in complex with uPA, 11 which it inhibits; hence, PCI is also referred to as plasminogen activator inhibitor-3 (PAI-3). However, the physiologic role of uPA inhibition by PCI in the urinary tract is unknown.It is known that metastasis and invasion of various tumor cells are mediated by uPA and its receptor. 12 uPA is inhibited by PAI-1 and PAI-2, 13 the former of which has been reported to be essential for regulation of tumor cell invasion and metastasis by promoting angiogenesis. 14,15 Previously, it was shown that the expression of uPA is lower, that the expression of uPA receptor is moderately higher and that the expression of PAI-1 is significantly higher in human renal cell carcinoma (RCC) than in nontumor kidney tissue. 16,17 Furthermore, Swiercz et al. 18 suggested that the expression of uPA, its receptor and PAI-1 correlate with the aggressive phenotype of RCC. These studies suggest the importance of the plasminogen activator system, including uPA, its receptor and PAI-1, in the process of RCC tumor cell invasion; however, there is no direct evidence yet that uPA regulates the invasiveness of RCC cells. It is also known that uPA and/or plasmin may ...

The present study clearly demonstrated that PTMA expression is intimately involved in the differentiation and progression of human prostate cancers, and could be a target for therapy and diagnostic purposes.

Protein C inhibitor (PCI) is the plasma serine protease inhibitor of activated protein C, the active enzyme of the anticoagulant protein C pathway. Recently, PCI was also detected in human seminal plasma and reproductive organs (testis, seminal vesicle and prostate) suggesting that PCI may also play an important role in the reproductive system. In this study, we cloned the full length of rat PCI cDNA, and determined its amino acid sequence and tissue distribution. We also evaluated the effect of androgen on PCI mRNA expression in seminal vesicles and testes. The isolated 2074-bp rat PCI cDNA was composed of a 47-bp 5P-non-coding region, a 1218-bp coding region of a 406-amino acid precursor protein, a stop codon and a 806-bp 3P-non-coding region. The deduced amino acid sequence of rat PCI showed 85.7%, 64.1% and 62.2% homology with that of mouse, rhesus monkey and human PCIs, respectively. Northern blot analysis showed that the rat PCI mRNA is expressed strongly in the seminal vesicle, moderately in the testis, but not in the liver. PCI mRNA expression in seminal vesicles and testes was found to increase during the process of development, suggesting that it is under androgen control. Subsequently, we examined the effect of castration and/or treatment with 17L L-estradiol or testosterone on PCI mRNA expression in the mature rat seminal vesicles. The PCI mRNA expression in seminal vesicles was significantly decreased after castration or 17L L-estradiol treatment. Testosterone itself did not affect PCI mRNA expression, but treatment in castrated rats significantly enhanced its mRNA expression. These findings suggest that the PCI gene expression in rat seminal vesicles is regulated by androgen.z 1998 Federation of European Biochemical Societies.

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