A Preclinical Model for ER alpha-Positive Breast Cancer Points to the Epithelial Microenvironment as Determinant of Luminal Phenotype and Hormone Response

作者：Sflomos George; Dormoy Valerian; Metsalu Tauno; Jeitziner Rachel; Battista Laura; Scabia Valentina; Raffoul Wassim; Delaloye Jean Francois; Treboux Assya; Fiche Maryse; Vilo Jaak; Ayyanan Ayyakkannu; Brisken Cathrin^*

来源：Cancer Cell, 2016, 29(3): 407-422.

DOI：10.1016/j.ccell.2016.02.002

Seventy-five percent of breast cancers are estrogen receptor a 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 TGF beta/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.

• 出版日期2016-3-14