Abstract P4-04-06: Histone H2A Inhibits Breast Cancer Stem Cell Growth
Notice bibliographique
Résumé
Abstract Introduction: Recent studies have identified epigenetic abnormalities as the underlying cause of many breast cancers. In particular, the aberrant acetylation of core histones may be a pivotal source of dysregulated expression of both oncogenes and tumour suppressor genes. Histone deacetylase inhibitors are known to restore histone acetylation and to induce cellular differentiation and growth arrest in breast cancer cells and are the object of extensive research for novel anticancer treatments. We hypothesize that acetylated proteins, in particular histone H2A, could also serve as an alternative substrate for histone deacetylase, thereby promoting cellular histone acetylation and arrest of cancer cell growth. Indeed, our previous results indicate that exogenous calf thymus histone H2A penetrates cells and their nuclei, and induces differentiation and senescence in human breast cancer cells. In contrast, human recombinant histone H2A and H2AX, which lack post-translational modifications, fail to yield these results in spite of the fact that human and bovine histone H2A are virtually identical in their amino acid sequences. However, these recombinant molecules were obtained from bacteria, which lack the intracellular machinery that is necessary to generate post-translational modifications. Thus, post-translational histone modifications are pivotal to the inhibition of breast cancer cell proliferation. Objective: We have extended our study to establish if exogenous calf thymus histone H2A could also induce growth arrest of breast cancer stem cells, and subsequently to determine which portion (s) of the histone H2A molecule is responsible for this action, using overlapping synthetic peptides. Materials and Methods: Breast cancer stem cells were incubated with exogenous calf thymus histone H2A and seven synthetic peptides corresponding to overlapping portions of the entire protein and include all of its post-translational modifications. Cellular morphology was observed and viable cells were counted using trypan blue exclusion. Control experiments were performed with normal breast cells, cells from fibrocystic breast tissues, and breast cancer cells that were not significantly enriched in cancer stem cells. Results and Discussion: Histone H2A inhibits breast cancer stem cell growth and increases their adhesion. Stem cells have recently been identified in many malignant tumours, including breast cancer. Since cancer stem cells are thought to be an important source of therapeutic resistance, they provide a novel research focus for alternative treatment strategies. Our results are very encouraging and may lead to the development of new pharmacological molecules targeting epigenetic abnormalities in breast cancer stem cells. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-04-06.
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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) | 0,001 | 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 | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,007 | 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 ».