A Preclinical Model for ERα-Positive Breast Cancer Points to the Epithelial Microenvironment as Determinant of Luminal Phenotype and Hormone Response.
- Sflomos G ISREC - Swiss Institute for Experimental Cancer Research, School of Life Sciences, Ecole polytechnique fédérale de Lausanne (EPFL), SV2.832 Station 19, 1015 Lausanne, Switzerland.
- Dormoy V ISREC - Swiss Institute for Experimental Cancer Research, School of Life Sciences, Ecole polytechnique fédérale de Lausanne (EPFL), SV2.832 Station 19, 1015 Lausanne, Switzerland.
- Metsalu T Institute of Computer Science, University of Tartu, Liivi 2, Tartu 50409, Estonia.
- Jeitziner R ISREC - Swiss Institute for Experimental Cancer Research, School of Life Sciences, Ecole polytechnique fédérale de Lausanne (EPFL), SV2.832 Station 19, 1015 Lausanne, Switzerland.
- Battista L ISREC - Swiss Institute for Experimental Cancer Research, School of Life Sciences, Ecole polytechnique fédérale de Lausanne (EPFL), SV2.832 Station 19, 1015 Lausanne, Switzerland.
- Scabia V ISREC - Swiss Institute for Experimental Cancer Research, School of Life Sciences, Ecole polytechnique fédérale de Lausanne (EPFL), SV2.832 Station 19, 1015 Lausanne, Switzerland.
- Raffoul W Lausanne University Hospital, 1011 Lausanne, Switzerland.
- Delaloye JF Lausanne University Hospital, 1011 Lausanne, Switzerland.
- Treboux A Lausanne University Hospital, 1011 Lausanne, Switzerland.
- Fiche M Lausanne University Hospital, 1011 Lausanne, Switzerland.
- Vilo J Institute of Computer Science, University of Tartu, Liivi 2, Tartu 50409, Estonia.
- Ayyanan A ISREC - Swiss Institute for Experimental Cancer Research, School of Life Sciences, Ecole polytechnique fédérale de Lausanne (EPFL), SV2.832 Station 19, 1015 Lausanne, Switzerland.
- Brisken C 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.
- 2016-03-08
Published in:
- Cancer cell. - 2016
Animals
Breast Neoplasms
Cell Line, Tumor
Estrogen Receptor alpha
Female
Humans
MCF-7 Cells
Mammary Glands, Human
Mice
Mice, Inbred NOD
Mice, SCID
Signal Transduction
Snail Family Transcription Factors
Transcription Factors
Transforming Growth Factor beta
Tumor Microenvironment
English
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.
- Language
-
- English
- Open access status
- bronze
- Identifiers
-
- DOI 10.1016/j.ccell.2016.02.002
- PMID 26947176
- Persistent URL
- https://sonar.ch/global/documents/182134
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