Abstract 86: Prolactin and testosterone induction of carboxypeptidase-D to promote cell survival is greater in prostate cancer cells than benign prostate cells, and their synergistic action in prostate cancer cells is effectively blocked by receptor antagonists Δ1-9-G129R and flutamide.
Notice bibliographique
Résumé
Abstract Introduction: Carboxypeptidase-D (CPD), a membrane-bound metalloproteinase, cleaves C-terminal arginine, which is the substrate of nitric oxide synthase for production of nitric oxide (NO). NO regulates many cellular processes including tumor progression. We have reported that CPD and NO levels were upregulated by testosterone (T) or prolactin (PRL) to enhance survival of prostate cancer (pCa) cells. This study further characterized T/PRL regulation of CPD expression. CPD and NO levels in benign and malignant prostate cells/tissues were compared to determine their roles in pCa development. Methods: Quantitative RT-PCR (QPCR) was used to measure CPD mRNA levels in human prostate cell lines. Immunohistochemistry (IHC) and tissue microarray (TMA) analysis were used to compare CPD staining in prostate specimens. NO production was measured using 4,5-diaminofluorescein diacetate (DAF-2DA) assay. Results: QPCR analysis showed that CPD mRNA levels were not significantly altered in the benign prostate cell lines BPH-1 and RWPE1, as compared to a 3-4-fold increase in the pCa cell line LNCaP, following T or PRL treatment (P<0.01, n=3-6). T or PRL caused similar increases in other pCa cell lines (22Rv1, MDAPCa2b and PC-3), in which the androgen receptor (AR) and/or PRL receptor (PRLR) were expressed. DAF-2DA assays showed that NO levels were increased <1.6-fold in benign cells, compared to >3.5-fold in LNCaP cells after T/PRL stimulation. In LNCaP cells, T and PRL acted synergistically to upregulate NO, but were maximally suppressed when both receptors were inhibited with flutamide and Δ1-9-G129R in combination. Consistent with these results, TMA analysis showed significantly increased CPD staining from 8.9±3.8% (mean±SEM, n=18) of benign epithelial cell area to 30.9±2.9% (n=79) of tumor cell area (P<0.001). Endothelial cells in blood vessels associated with tumor were more likely to show positive staining than vessels of benign tissue (P<0.0001). A second TMA also showed increased CPD staining from 5.6±0.9% (n=48) in benign prostatic hyperplasia (BPH) to 17.9±2.1% (n=88) in pCa. TMA results were corroborated by IHC assessment of large (≥50mm2) prostate tissues from 35 men, where CPD staining increased from 13.1±2.9% in BPH to 29.5±4.4% in pCa. Conclusion: T/PRL-stimulated CPD mRNA levels were higher in tumor than in benign prostate cell lines. Likewise, CPD protein levels were higher in cancer than benign prostate specimens. Elevated CPD levels increased NO production, which was maximally suppressed when both the AR and PRLR were inhibited. Our results suggest that inhibition of both the AR and PRLR may be a more effective treatment for pCa and implicate the potential usefulness of the CPD-Arg-NO pathway as a therapeutic target for pCa. Citation Format: Catherine K. L. Too, Lynn N. Thomas, Jennifer Merrimen. Prolactin and testosterone induction of carboxypeptidase-D to promote cell survival is greater in prostate cancer cells than benign prostate cells, and their synergistic action in prostate cancer cells is effectively blocked by receptor antagonists Δ1-9-G129R and flutamide. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 86. doi:10.1158/1538-7445.AM2013-86
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,001 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,007 | 0,002 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».