Carboxypeptidase-D is elevated in prostate cancer and its anti-apoptotic activity is abolished by combined androgen and prolactin receptor targeting

摘要: BACKGROUND Carboxypeptidase-D (CPD) cleaves C-terminal arginine for nitric oxide (NO) production. CPD and NO levels are upregulated by testosterone (T) prolactin (PRL) to promote survival of prostate cancer (pCa) cells. This study evaluated immunostaining T/PRL regulation in benign malignant tissues/cells determine the role pCa. METHODS Immunohistochemistry (IHC) tissue microarrays (TMA) were used specimens. QPCR immunoblotting quantify mRNA/protein expression production was measured using 4,5-diaminofluorescein diacetate assay. RESULTS CPD staining increased from 8.9 ± 3.8% (Mean ± SEM, n = 15) epithelial cell area 30.9 ± 2.9% (n = 30) tumor one set TMAs (P = 0.0008) 5.9 ± 0.9% (n = 45) 18.8 ± 1.9% (n = 55) another (P < 0.0001). IHC tissues (≥50 mm2) confirmed staining, 13.1 ± 2.9% (n = 16) 29.5 ± 4.4% pCa (n = 31, P = 0.0095). T and/or PRL several but not lines. acted synergistically increase production, which abolished only when receptor antagonists flutamide Δ1–9-G129R-hPRL together. CONCLUSIONS CPD T/PRL-stimulated higher than tissues/cells. Elevated both AR PRLR inhibited. Our implicates a critical CPD-Arg-NO pathway progression, suggests that AR+PRLR inhibition is more effective treatment pCa. Prostate 74:732–742, 2014. © 2014 Wiley Periodicals, Inc.