Copyright © 2008 Cell Press. All rights reserved.
Cancer Cell, Vol 13, 394-406, 06 May 2008
Article
Regulation of In Situ to Invasive Breast Carcinoma Transition
1 Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA
2 Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA
3 Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA
4 Harvard Medical School, Boston, MA 02115, USA
5 Department of Biostatistics, Harvard School of Public Health, Boston, MA 02115, USA
6 Biogen-Idec, Cambridge, MA 02142, USA
7 GeneGo, Inc., St. Joseph, MI 49085, USA
8 Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110, USA
9 Department of Pathology, Beth-Israel Deaconess Medical Center, Boston, MA 02115, USA
10 Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA
∗Corresponding author
Kornelia Polyak
kornelia_polyak@dfci.harvard.edu
Summary
The transition of ductal carcinoma in situ (DCIS) to invasive carcinoma is a poorly understood key event in breast tumor progression. Here, we analyzed the role of myoepithelial cells and fibroblasts in the progression of in situ carcinomas using a model of human DCIS and primary breast tumors. Progression to invasion was promoted by fibroblasts and inhibited by normal myoepithelial cells. Molecular profiles of isolated luminal epithelial and myoepithelial cells identified an intricate interaction network involving TGFβ, Hedgehog, cell adhesion, and p63 required for myoepithelial cell differentiation, the elimination of which resulted in loss of myoepithelial cells and progression to invasion.
