Upregulation of STAT1 transcription activator by an androgen agonist in prostate cancer cells affects intracellular cholesterol esterification
Notice bibliographique
Résumé
LB-197 The objective of this work was to determine the effect of an androgen agonist, R1881, on intracellular cholesterol synthesis and esterification within an androgen-dependent prostate cancer cell line. We investigated the activity (using standardized radiolabeled techniques) and expression (Western Blot) of two cholesterol metabolism enzymes, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and acyl-coenzyme A:cholesterol acyltransferase (ACAT), in the LNCaP androgen-dependent prostate cancer cell model and in the PC-3 androgen-independent model for comparison. At the cellular level, when PC-3 and LNCaP cell lysates were examined for free cholesterol and cholesteryl ester content using prepared enzymatic kits, we found a decrease in free cholesterol and an increase in cholesteryl esters in LNCaP cells treated with the androgen receptor agonist R1881, compared to controls. In the PC-3 cells we did not find a change in total cholesterol or in cholesteryl esters upon R1881 treatment. HMG-CoA reductase activity in the LNCaP and PC-3 cells was increased upon androgen stimulation. Furthermore, HMG-CoA reductase protein expression in PC-3 was higher than in LNCaP cells. The increased intracellular cholesteryl ester levels found in R1881-treated LNCaP cells were not associated with an increased in vitro ACAT activity. In contrast, we found an increase in ACAT activity upon androgen stimulation in PC-3 cells. We analyzed the expression of the two ACAT isoforms, ACAT1 and ACAT2 to determine if their protein levels were affected by the R1881 treatment in both cell lines. We found that ACAT2 expression was induced in LNCaP cells treated with R1881. In the case of PC-3, ACAT1 expression was induced when the cells were treated with the androgen agonist. We investigated the mechanism of ACAT1 induction in PC-3 cells and assessed the expression of STAT1α, a transcriptional activator that modulates ACAT1 expression. We found that STAT1α expression and phosphorylation were induced by R1881 treatment in PC-3; thus it is a possible mechanism to account for increased ACAT1 expression in PC-3 cells. Induction of STAT1α activation may lead to an increase in ACAT1 protein expression which was associated with augmented ACAT activity in PC-3 cells. Interestingly this increased ACAT activity was not associated with increased cholesteryl ester accumulation in PC-3 cells treated with R1881, suggesting that other mechanisms such as cholesterol esterases or cholesteryl ester secretion may contribute to cholesteryl ester homeostasis in prostate cells. Taken together, these findings further support the importance of cholesterol metabolism regulation within prostate cancer cells. Furthermore, they also unravel a novel role for STAT1α in prostate cancer metabolism.
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 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,001 |
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 ».