A Preclinical Model for ERα-Positive Breast Cancer Points to the Epithelial Microenvironment as Determinant of Luminal Phenotype and Hormone Response.
Fiche publication
Date publication
mars 2016
Journal
Cancer cell
Auteurs
Membres identifiés du Cancéropôle Est :
Dr DORMOY Valerian
Tous les auteurs :
Sflomos G, Dormoy V, Metsalu T, Jeitziner R, Battista L, Scabia V, Raffoul W, Delaloye JF, Treboux A, Fiche M, Vilo J, Ayyanan A, Brisken C
Lien Pubmed
Résumé
Seventy-five percent of breast cancers are estrogen receptor α positive (ER⁺). Research on these tumors is hampered by lack of adequate in vivo models; cell line xenografts require non-physiological hormone supplements, and patient-derived xenografts (PDXs) are hard to establish. We show that the traditional grafting of ER⁺ tumor cells into mammary fat pads induces TGFβ/SLUG signaling and basal differentiation when they require low SLUG levels to grow in vivo. Grafting into the milk ducts suppresses SLUG; ER⁺ tumor cells develop, like their clinical counterparts, in the presence of physiological hormone levels. Intraductal ER⁺ PDXs are retransplantable, predictive, and appear genomically stable. The model provides opportunities for translational research and the study of physiologically relevant hormone action in breast carcinogenesis.
Mots clés
Animals, Breast Neoplasms, genetics, Cell Line, Tumor, Estrogen Receptor alpha, genetics, Female, Humans, MCF-7 Cells, Mammary Glands, Human, pathology, Mice, Mice, Inbred NOD, Mice, SCID, Signal Transduction, genetics, Snail Family Transcription Factors, Transcription Factors, genetics, Transforming Growth Factor beta, genetics, Tumor Microenvironment, genetics
Référence
Cancer Cell. 2016 Mar 14;29(3):407-422