Abstract LB-269: A new role for the gain-of-function activity of p53 in breast cancer
Notice bibliographique
Résumé
Abstract Using tissue microarrays constructed from samples obtained from normal breast tissues and breast carcinomas, we previously found that galectin-7 is specifically expressed in myoepithelial cells but not luminal cells. We also found that abnormally high levels of galectin-7 were restricted to basal-like breast cancers, a heterogeneous group of cancers with a poor prognosis. These results were consistent with the genomic profiling data previously reported by the group of Charles Perou who recently provided a molecular portrait of human breast tumors. Their data revealed that while galectin-7 transcripts were expressed at low levels in normal breast tissues and mammary epithelial cell lines, they were highly expressed in estrogen receptor (ER)-negative breast cancer. Our data were also consistent with microarray studies by Jones and colleagues who identified galectin-7 as a myoepithelial-specific genes. In fact, galectin-7 ranked first on a list of 42 most predictive genes that distinguish luminal and myoepithelial cells. This expression of galectin-7 is not only important to study in terms of biomarkers of aggressive forms of breast cancer, but also because increased galectin-7 in breast cancer cells is known to increase their metastatic behavior. However, the expression of galectin-7 in aggressive forms of breast cancer is somewhat paradoxical if not surprising because galectin-7 has been considered an apoptosis regulator under the control of p53. In a previous report, Galectin-7 (also called p53-induced gene 1) was found to be one of the 14 transcripts that were induced by wild-type p53 in colon cancer cells. Here, we have examined this apparent contradiction by investigating the molecular mechanisms controlling galectin-7 expression in human breast cancer cells. We found that galectin-7 expression in human breast cancer cells is dictated by a gain-of-function activity of mutant p53. This conclusion is based on the following: 1) expression of galectin-7 in cancer cell lines correlated with constitutively high levels of NF-κB activity; 2) transfection of NF-κB subunits or treatment of cells with TNFα, a well-known inducer of NF-κB, increased endogenous level of galectin-7; 3) inhibitors of NF-κB reduced constitutive galectin-7 expression; 4) transfection of a transcriptionally inactive form of p53 (R175H) into a p53-null human breast cancer cell line induced galectin-7 via increased NF-kB activity. These findings identify galectin-7 as a novel player through which mutp53 exerts its gain-of-function activity in breast cancer cells. 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 LB-269. doi:1538-7445.AM2012-LB-269
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 | 0,001 | 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 | 0,000 |
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 ».