title: A Preclinical Model for ERα-Positive Breast Cancer Points to the Epithelial Microenvironment as Determinant of Luminal Phenotype and Hormone Response.
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.
authors.affiliation: ISREC - Swiss Institute for Experimental Cancer Research, School of Life Sciences, Ecole polytechnique fédérale de Lausanne (EPFL), SV2.832 Station 19, 1015 Lausanne, Switzerland.
authors.forename: George
authors.initials: G
authors.lastname: Sflomos
authors.affiliation: ISREC - Swiss Institute for Experimental Cancer Research, School of Life Sciences, Ecole polytechnique fédérale de Lausanne (EPFL), SV2.832 Station 19, 1015 Lausanne, Switzerland.
authors.forename: Valerian
authors.initials: V
authors.lastname: Dormoy
authors.affiliation: Institute of Computer Science, University of Tartu, Liivi 2, Tartu 50409, Estonia.
authors.forename: Tauno
authors.initials: T
authors.lastname: Metsalu
authors.affiliation: ISREC - Swiss Institute for Experimental Cancer Research, School of Life Sciences, Ecole polytechnique fédérale de Lausanne (EPFL), SV2.832 Station 19, 1015 Lausanne, Switzerland.
authors.forename: Rachel
authors.initials: R
authors.lastname: Jeitziner
authors.affiliation: ISREC - Swiss Institute for Experimental Cancer Research, School of Life Sciences, Ecole polytechnique fédérale de Lausanne (EPFL), SV2.832 Station 19, 1015 Lausanne, Switzerland.
authors.forename: Laura
authors.initials: L
authors.lastname: Battista
authors.affiliation: ISREC - Swiss Institute for Experimental Cancer Research, School of Life Sciences, Ecole polytechnique fédérale de Lausanne (EPFL), SV2.832 Station 19, 1015 Lausanne, Switzerland.
authors.forename: Valentina
authors.initials: V
authors.lastname: Scabia
authors.affiliation: Lausanne University Hospital, 1011 Lausanne, Switzerland.
authors.forename: Wassim
authors.initials: W
authors.lastname: Raffoul
authors.affiliation: Lausanne University Hospital, 1011 Lausanne, Switzerland.
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Delaloye
authors.affiliation: Lausanne University Hospital, 1011 Lausanne, Switzerland.
authors.forename: Assya
authors.initials: A
authors.lastname: Treboux
authors.affiliation: Lausanne University Hospital, 1011 Lausanne, Switzerland.
authors.forename: Maryse
authors.initials: M
authors.lastname: Fiche
authors.affiliation: Institute of Computer Science, University of Tartu, Liivi 2, Tartu 50409, Estonia.
authors.forename: Jaak
authors.initials: J
authors.lastname: Vilo
authors.affiliation: ISREC - Swiss Institute for Experimental Cancer Research, School of Life Sciences, Ecole polytechnique fédérale de Lausanne (EPFL), SV2.832 Station 19, 1015 Lausanne, Switzerland.
authors.forename: Ayyakkannu
authors.initials: A
authors.lastname: Ayyanan
authors.affiliation: ISREC - Swiss Institute for Experimental Cancer Research, School of Life Sciences, Ecole polytechnique fédérale de Lausanne (EPFL), SV2.832 Station 19, 1015 Lausanne, Switzerland. Electronic address: cathrin.brisken@epfl.ch.
authors.forename: Cathrin
authors.initials: C
authors.lastname: Brisken
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D042361:Mammary Glands, Human / Q000473:pathology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D015398:Signal Transduction / Q000235:genetics; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics; D059016:Tumor Microenvironment / Q000235:genetics*
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; C000604407:SNAI1 protein, human; C000604449:Snai2 protein, mouse; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D016212:Transforming Growth Factor beta