Elucidating the Transcriptional Regulatory Roles of STAT3 and FOXA1 Transcription Factors in Genetically Engineered Mouse Models of Human Breast Cancer
Notice bibliographique
Résumé
Breast cancer is the predominant cancer type among Canadian women, with a striking incidence rate of one in eight women during their lifetime. Transcription factors play pivotal roles in breast cancer initiation and progression. Signal transducer and activator of transcription 3 (Stat3) is a transcription factor that mediates the expression of a variety of genes in response to cytokines and growth factors. The activation of Stat3 plays key roles in cell growth, survival and apoptosis, cell migration and invasion, and inflammation. Using the conditional Stat3 knockout mouse model, our lab previously demonstrated that Stat3 deficiency can impede the metastasis of ErbB2-positive breast cancer. However, the mechanism remains unclear. By doing transcriptomic analysis of Stat3-null and wildtype ErbB2 positive breast cancer cells dissociated from mouse tumors, Lgals3 turned out to be a target of Stat3 that could have mediated the metastatic phenotype. Upon shRNA knockdown of Lgals3, ErbB2 positive breast cancer cells demonstrated dramatically reduced migration and invasion. They also formed elevated levels of focal adhesions that may lead to reduced migration and metastasis. Furthermore, the pharmacological inhibition of Gal-3 leads to decreased cell migration and invasion. This reveals the therapeutic potential of Lgals3 inhibition in ErbB2-Positive breast cancer metastasis prevention. Estrogen receptor (ER) positive breast cancer accounts for about 70% of total breast cancer and metastatic ER-Positive breast cancer accounts for the majority of breast cancer mortality. Although ER-Positive breast cancer is the most common subtype of breast cancer, there is a lack of mouse models that faithfully recapitulate ER-driven breast cancer. Published research from our lab has shown that knock-in mutation of ESR1Y541S results in constitutive activation of ER, abnormal mammary gland development, male mouse feminization, and decreased survival, but no tumor growth is associated with this mouse model. Forkhead box protein A1 (FOXA1) is a transcription factor that facilitates ER-chromatin association, and promotes tumorigenesis through a variety of mechanisms. By overexpressing FOXA1 in the doxycycline-inducible mouse model named FIC/MTB and crossing it to ESR1 mouse model (FIC/MTB/ESR1), we may be able to create a novel ER-Positive breast cancer mouse model. We demonstrated that FIC/MTB mouse mammary gland-derived organoids developed a filled sphere structure upon doxycycline induction, mimicking human mammary gland hyperplasia. Moreover, the FIC/MTB/ESR1 mice developed significant hyperplasia after 20-week induction. Although in vivo tumor kinetics study is ongoing, our current findings suggest that the novel mouse model FIC/MTB/ESR1 has the potential to develop mammary tumors
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 distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| 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) | 0,000 | 0,000 |
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 tête enseignante, 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 ».