Reconstruction of functionally normal and malignant human breast tissues in mice
- Charlotte Kuperwasser*,†,
- Tony Chavarria*,
- Min Wu‡,
- Greg Magrane§,
- Joe W. Gray§,
- Loucinda Carey*,
- Andrea Richardson¶, and
- Robert A. Weinberg*
- *Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142; ‡GenPath Pharmaceuticals, Incorporated, 300 Technology Square, 7th Floor, Cambridge, MA 02139; §University of California San Francisco Comprehensive Cancer Center, 2340 Sutter Street, Room N415, San Francisco, CA 94143-0808; and ¶Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, MA 02115
-
Contributed by Robert A. Weinberg, February 13, 2004
Abstract
The study of normal breast epithelial morphogenesis and carcinogenesis in vivo has largely used rodent models. Efforts at studying mammary morphogenesis and cancer with xenotransplanted human epithelial cells have failed to recapitulate the full extent of development seen in the human breast. We have developed an orthotopic xenograft model in which both the stromal and epithelial components of the reconstructed mammary gland are of human origin. Genetic modification of human stromal cells before the implantation of ostensibly normal human mammary epithelial cells resulted in the outgrowth of benign and malignant lesions. This experimental model allows for studies of human epithelial morphogenesis and differentiation in vivo and underscores the critical role of heterotypic interactions in human breast development and carcinogenesis.
Footnotes
-
↵ † To whom correspondence should be sent at the present address: Department of Physiology, Tufts University School of Medicine, 136 Harrison Avenue 701, Boston, MA 02111. E-mail: charlotte.kuperwasser{at}tufts.edu.
-
Abbreviations: MEC, mammary epithelial cell; HGF, hepatocyte growth factor; PCNA, proliferating cell nuclear antigen; FISH, fluorescence in situ hybridization; TDLU, terminal ductal lobular units; TGF-β, transforming growth factor β; RMF/EG, reduction mammary fibroblasts immortalized with human telomere and GFP.
-
See Commentary on page 4723.
- Copyright © 2004, The National Academy of Sciences
