Abstract 5116: The calcium channel subunit CACNG4 plays a role in breast cancer metastasis.
Notice bibliographique
Résumé
Abstract Introduction: Previously, we used aCGH to analyze genomic alterations in primary breast tumors with and without lymph node (LN) metastasis. A significant correlation was found between gain of chromosome 17q24 and LN metastasis. Selected genes including L-type calcium channel voltage dependent gamma subunit 4 (CACNG4) were further validated for increased protein expression in invasive breast tumors. CACNG4 is involved in calcium channel regulation in excitable cells of muscles and the brain. It is the only gamma subunit that also shows expression in non-excitable cells, such as glial and intestinal epithelial cells, suggestive of additional functions. It is over-expressed in glioblastoma multiforme cell lines resistant to EGFR inhibitors. Breast cancer gene expression datasets (NKI and IPC) identified an association of CACNG4 expression with LN metastasis and ER positivity. In the present study, we characterized CACNG4 in breast cancer with particular attention to its metastasis-related ability. Methodology: RNA interference was used for knockdown studies in cell lines followed by cell migration, invasion, aggregation and adhesion assays. Intracellular calcium influx in response to calcium channel agonists and antagonists was measured using the Fluo-4 calcium indicator dye. Results: CACNG4 showed variable expression across a panel of breast cancer cell lines. MCF10A (a non malignant cell line) does not express CACNG4, while it is highly expressed in ER positive cell lines (MCF7, MDA-MB-361, CAMA1) and lower in EGFR high cell lines (MDA-MB-468 and MDA-MB-231). CACNG4 knockdown inhibited cell migration and invasion in MCF7 and MDA-MB-231 cells. Conversely, cell adhesion and cell-cell aggregation was increased. RT-PCR revealed an inverse relation between CACNG4 expression and PKC-zeta specifically, which is involved in tight junction formation and shows low expression in breast, prostate and renal cancers. Thus, CACNG4 may play a role in de-adhesion and cell dissemination during metastasis. Blocking calcium channels with amlopidine had an anti-proliferative affect. Serum stimulation of EGFR high cell lines resulted in calcium influx, that was blocked in a dosage dependent manner with amlodipine, and synergistically blocked further with the EGFR specific tyrosine kinase inhibitor tryphostin AG1478. Knockdown of CACNG4 resulted in increased calcium influx suggesting a role in keeping the channel closed. Cells also showed resistance to amlodipine, requiring higher doses to block calcium influx. Conclusions: L-type channels are active in non-excitable breast cancer cells, and are affected by EGFR activity. CACNG4 maintains these channels in a closed state, modulating calcium influx, and inhibiting PKC-zeta expression which may result in metastatic function. The ability of calcium channel blockers to target channels in a CACNG4 dependent manner suggests novel treatment possibilities for invasive breast cancer. Citation Format: Nisha Kanwar, Ranju Nair, Dong-Yu Wang, Susan J. Done. The calcium channel subunit CACNG4 plays a role in breast cancer metastasis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5116. doi:10.1158/1538-7445.AM2013-5116
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 | 0,001 |
| 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) | 0,004 | 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 ».