Abstract P4-03-02: Establishing a Relationship between Breast Cancer, Prolactin and Altered Fat Metabolism
Notice bibliographique
Résumé
Abstract Despite decades of research, breast cancer remains one of the most common cancers world-wide. Mammary carcinoma has been associated with a high-fat diet, and its rate in overweight post-menopausal women is up to 50% higher than in normal-weight women. The current study examined breast cancer as a metabolic disease in the context of altered fat catabolism, with a focus on examining the effects of prolactin (PRL) on the adenosine 5'-monophosphate-activated protein kinase (AMPK) energy sensing pathway that culminates with carnitine palmitoyl transferase 1 (CPT1), an enzyme that shuttles long-chain fatty acids into the mitochondrial matrix for beta oxidation. When a cell has high energy demands or is stressed, AMPK activation leads to either increased glucose uptake or the phosphorylation of acetyl-CoA carboxylase (ACC), resulting in a reduction in malonyl-CoA levels that lift an allosteric inhibition on CPT1, in turn leading to an increase in CPT1 enzyme activity. Conversely, increased malonyl-CoA levels, together with increased fatty acid synthase activity, favor lipogenesis. PRL has been shown to affect fat metabolism in adipocytes by altering malonyl-CoA levels, and we therefore examined whether CPT1 expression was altered in breast cancer cells in response to treatment with recombinant human PRL. The metabolic effects of this hormone, which is normally produced in breast tissue and has been epidemiologically linked with breast cancer, were investigated in a normal human breast epithelial cell line (184B5) and in breast cancer cells. PRL up-regulated CPT1 expression at both the mRNA and protein levels in cancer cells, but not in 184B5 cells. Of note, compared to MCF-7 or MDA-MB-231 cells, T47D cells expressed the highest levels of CPT1. The 85 kDa PRL receptor isoform was also highly expressed in this cell line compared to 184B5 or MCF-7 cells. Furthermore, PRL dose-dependently increased CPT1 enzyme activity in T47D cells, also inducing the phosphorylation of both the AMPKα catalytic subunit at threonine 172 and ACC. In T47D cells treated with AMPKα siRNA, transient knock-down of the catalytic AMPK subunit correlated with a similar knock-down in CPT1 mRNA levels. CPT1 levels in the knock-down cells could not be restored by treatment with PRL, suggesting that the PRL-mediated effect requires activation of the AMPK pathway. We also demonstrated that treatment with PRL leads to the phosphorylation of TAK1 and LKB1, two kinases that are known to activate AMPKα. It is known that PRL contributes to breast cancer by inducing cell proliferation, survival, motility, and angiogenesis. Our work proposes a novel role for this hormone in mammary carcinogenesis through its effect on fat metabolism via the induction of the AMPK pathway. Elucidating how breast cancer cells differentially produce and utilize energy compared to normal breast epithelial cells may lead to the development of new therapies for the treatment or improved management of this complex disease. (Research supported by Canadian Institutes of Health Research.) Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-03-02.
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 | 0,001 |
| 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) | 0,005 | 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 ».