Prolactin‐ and testosterone‐induced carboxypeptidase‐D correlates with increased nitrotyrosines and Ki67 in prostate cancer

摘要: BACKGROUND Carboxypeptidase-D (CPD) cleaves C-terminal arginine for conversion to nitric oxide (NO) by synthase (NOS). Prolactin (PRL) and androgens stimulate CPD gene transcription expression, which increases intracellular production of NO promote viability prostate cancer (PCa) cells in vitro. The current study evaluated whether hormonal upregulation PCa cell viabilty vivo, correlating changes expression nitrotyrosine residues (products action) with proliferation marker Ki67 associated proteins during development progression. METHODS Fresh tissues, obtained from 40 men benign prostatic hyperplasia (BPH) or PCa, were flash-frozen at the time surgery used RT-qPCR analysis CPD, androgen receptor (AR), PRL (PRLR), eNOS, levels. Archival paraffin-embedded tissues 113 BPH immunohistochemical (IHC) nitrotyrosines, phospho-Stat5 (for activated PRLR), AR, eNOS/iNOS, Ki67. RESULTS RT-qPCR IHC analyses showed strong AR PRLR malignant prostates. mRNA levels increased ∼threefold compared BPH, corresponded a twofold increase progressive 11.4 ± 2.1% 21.8 ± 3.2% low-grade (P = 0.007), 40.7 ± 4.0% high-grade (P < 0.0001) 50.0 ± 9.5% castration-recurrent (P < 0.0001). Immunostaining nitrotyrosines mirrored these progression. tended co-localize, as did phospho-Stat5. CONCLUSIONS CPD, nitrotyrosine, higher than along phospho-Stat5. correlation combined abundant PRLR, supports vitro evidence that CPD-Arg-NO pathway is involved regulation proliferation. It further highlights role progression PCa. Prostate 75:1726–1736, 2015. © 2015 Wiley Periodicals, Inc.