Abstract 5157: Prolactin plays a role in regulating fatty acid synthesis and metabolism in the prostate cancer cell line PC-3
Notice bibliographique
Résumé
Abstract Introduction: Prostate cancer (PCa) metabolism is unique from other cancers due to a high reliance on fatty acid (FA) break down for energy. This phenomenon of FA dependence is exemplified clinically by poor tumor detection by PET scanning, which makes proteins involved in FA synthesis and metabolism interesting therapeutic targets in PCa. Two important proteins for fat metabolism are fatty acid synthase (FASN) and carnitine palmitoyl-transferase I (CPT1). FASN is responsible for de novo synthesis of long-chain (LC) FA and its activation is tightly regulated. CPT1 is a rate-limiting enzyme, which shuttles LC-FA into the mitochondria for beta-oxidation. The hormone prolactin (PRL) plays a role in the normal prostate by increasing energy metabolism and citrate production. The receptor for PRL (PRLR) has 5 isoforms, which are speculated to have different signaling capabilities. Our lab has shown the ability of PRL to increase CPT1A, but not FASN, mRNA and protein levels in human breast cancer cells. We hypothesized that PRL plays a similar role in PCa FA synthesis and metabolism due to the known presence of PRLR in these cells. The objectives of this study were to 1) identify which PRLR isoforms are expressed 2) determine if mRNA or protein levels of FASN and CPT1A change in response to PRL dosing and 3) establish if PRLR isoform expression plays a role in the results obtained in objective #2. Methods: PNT1A (normal prostate epithelial) and PC-3 (PCa) cells were dosed with 0, 50 or 100 ng/ml PRL. The mRNA levels for CPT1A and FASN were measured with RT-qPCR. For protein expression of FASN and CPT1A 30 ug of protein was loaded onto SDS-PAGE gels, followed by transfer to PVDF membranes, incubated in primary and then secondary antibodies and finally ECL reagent was added to the membranes for band detection. Over-expression studies were performed using lipofectamine 2000 to transiently over-express the long form or a shorter truncated version of the PRLR that were cloned into an expression vector. Over-expression studies were analyzed using Western blotting for FASN and CPT1A as mentioned above. Results: Both PNT1A and PC-3 cell lines express various PRLR isoforms. PRL did not have a significant effect on FASN or CPT1A mRNA levels in either cell type. Western blotting revealed significant changes for FASN and CPT1A protein levels in PC-3 cells at the 100 ng/ml dose. PRLR isoform over-expression studies indicated that isoform expression does appear to be an important variable in how PRL affects FASN and CPT1A protein levels. Conclusion: This project indicates a role for PRL in regulating FA synthesis and metabolism in the PCa cell line PC-3. Regulation at the protein level appears to be influenced by the PRLR isoform that is predominately expressed. These results suggest that PRL and/or its receptors could be a therapeutic target in treating prostate cancer. This project was supported by funding provided from CIHR to GS. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5157. doi:1538-7445.AM2012-5157
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 | 0,000 |
| 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) | 0,004 | 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 ».