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

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

Cancer Cell. 2016 Mar 1;

Authors: 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

Abstract
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.

PMID: 26947176 [PubMed - as supplied by publisher]

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