Abstract P5-05-01: IGFBP-7 Reduces Growth of Xenografted Breast Tumors in Mice and Inhibits Breast Cancer Cell Proliferation and Migration through the MEK-ERK Pathway
Notice bibliographique
Résumé
Abstract To identify genes correlated with breast tumorigenesis and eventual metastasis, gene expression profiles were generated using 28K whole genome microarrays. Gene expression profiles of primary breast tumors that grew and metastasized in the NOD/SCID mice were compared with other primary breast tumors that had different growth and metastatic potentials. Five hundred and eighty two genes were significantly differentially expressed by our statistical comparison criteria using the GeneSpring GX 7.3.1 software suite. In the metastatic set eight genes were selectively overexpressed (YB1, MMP7, MMP9, RAB5A, RABGDIB, EPHRB3, WNT2B, CSF1R) and 12 were selectively underexpressed (IGFBP7, GATA3, CST5, CDK6, SERBP1, MGP, TGF1L4, ESE3, ELF3, EDNRB, HECTD1, TINP1). In the present study we focused on the IGFBP-7 gene product which was found to be inversely correlated with disease progression in breast cancer. To further investigate the role of IGFBP-7 in breast tumor suppression, it was overexpressed in the triple negative MDA-MB-468 human breast cancer line. Ectopic overexpression of IGFBP-7 clearly reduced the growth of the MDA-MB-468/IGFBP-7 cells compared to the parental MDA-MB-468 cells. Ectopic overexpression or addition of rIGFBP-7 to breast cancer cell lines in vitro clearly reduced the growth of several breast cancer cell lines and resulted in phenotypic changes characterized by cell aggregation. Investigation of downstream signalling pathways affected by IGFBP-7 revealed that addition of IGFBP-7 to a triple negative breast cancer cell line not only inhibited phosphorylation of ERK-1/2 but also increased expression of the cyclin-dependent kinase inhibitor 1, p21. Similar IGFBP-7 treatment of an ER+ breast cancer line resulted not only in inhibition of ERK-1/2 phosphorylation, but also AKT phosphorylation, suggesting that IGFBP-7 may affect multiple pathways in hormone responsive breast cancer cell lines. IGFBP-7 protein is processed into a shorter form by matriptase. Breast cancer cell lines which were unable to process IGFBP-7 into the shorter form were unaffected by IGFBP-7 mediated growth inhibition, suggesting that cleaved IGFBP-7 may be required for growth inhibitory effects. When injected subcutaneously into NOD/SCID mice, the increased expression of IGFBP-7 in the MDA-MB-468/IGFBP-7 cells reduced the rate of tumor growth in comparison to the parental MDA-MB-468 cells. Furthermore, injection of rIGFBP-7 protein at the tumor site into breast cancer xenografted NOD/SCID mice also resulted in significant tumor growth reduction. These results suggest that the growth of breast cancer could be prevented by the forced expression of IGFBP-7 protein. Work in progress will further uncover the mechanism of IGFBP-7-mediated inhibition on signalling pathways, as well as differentiate the impact of both full length and cleaved IGFBP-7 protein on breast tumor inhibition. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-05-01.
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) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,001 | 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) | 0,006 | 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 ».