Protein C inhibitor (plasminogen activator inhibitor-3) expression in the CWR22 prostate cancer xenograft.
The serine protease inhibitor (serpin) protein C inhibitor (PCI) has been found in the prostate and possibly is a marker to distinguish normal prostate, benign prostatic hyperplasia, and prostate cancer. In this study, we assessed PCI expression in normal, hyperplastic, and malignant prostatic tissues, prostate cancer cell lines, and the CWR22 prostate cancer xenograft model that allowed us to study PCI expression and its regulation in response to androgens. By Northern blot, immunohistochemistry, and in situ hybridization, we found that PCI was expressed in both benign and malignant prostate tissues. Protein C inhibitor was expressed in both androgen-independent (PC-3) and androgen-dependent (LNCaP) prostate cancer cell lines. Furthermore, PCI was detected in all CWR22 tumor samples (androgen dependent, 6 days post-castration, 12 days post-castration followed by 72 h of testosterone treatment, and recurrent CWR22 tumor), although expression of the mature forms of both prostate-specific antigen (PSA) and its homolog, kallikrein 2 (hK2), was clearly androgen-dependent. These results suggest that PCI expression is not regulated by androgens and that PCI is unlikely to be a tumor suppressor gene, but also that PCI may be involved in regulating key serine proteases involved in metastatic prostate disease.
Glasscock
Laura N
LN
Department of Pathology and Laboratory Medicine, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7035, USA.
Réhault
Sophie M
SM
Gregory
Christopher W
CW
Cooper
Scott T
ST
Jackson
Tracy P
TP
Hoffman
Maureane
M
Church
Frank C
FC
D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis*; D015152:Blotting, Northern; D045744:Cell Line, Tumor; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D018046:Protein C Inhibitor / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014183:Transplantation, Heterologous
D014408:Biomarkers, Tumor; D018046:Protein C Inhibitor