Stem Cell Reviews

, Volume 3, Issue 2, pp 157–168

Wnt Signaling, Stem Cells, and the Cellular Origin of Breast Cancer

  • Charlotta Lindvall
  • Wen Bu
  • Bart O. Williams
  • Yi Li

DOI: 10.1007/s12015-007-0025-3

Cite this article as:
Lindvall, C., Bu, W., Williams, B.O. et al. Stem Cell Rev (2007) 3: 157. doi:10.1007/s12015-007-0025-3


The breast epithelium comprises cells at different stages of differentiation, including stem cells, progenitor cells, and more differentiated epithelial and myoepithelial cells. Wnt signaling plays a critical role in regulating stem/progenitor cells in the mammary gland as well as other tissue compartments. Furthermore, there is strong evidence suggesting that aberrant activation of Wnt signaling induces mammary tumors from stem/progenitor cells, and that Wnt exerts its oncogenic effects through LRP5/6-mediated activation of β-catenin and mTOR pathways. Recent studies using avian retrovirus-mediated introduction of oncogenes into a small subset of somatic mammary cells suggest that polyoma middle T antigen (PyMT) may also preferentially transform stem/progenitor cells. These observations suggest that stem/progenitor cells in the mammary gland may be especially susceptible to oncogenic transformation. Whether more differentiated cells may also be transformed by particular oncogenes is actively debated; it is presently unclear whether stem cells or differentiated mammary cells are more susceptible to transformation by individual oncogenes. Better stem cell and progenitor cell markers as well as the ability to specifically target oncogenes into different mammary cell types will be needed to determine the spectrum of oncogene transformation for stem cells versus more differentiated cells.


Stem cellWntBreast cancerMammary glandmTORPyMTtvaRCASTransgenicMouse model



low-density lipoprotein receptor-related protein


mammalian target of rapamycin


Frizzled-related protein


tumor virus A


mouse mammary tumor virus


whey acidic protein


polyoma middle T antigen


smooth muscle actin


replication-competent, ALV-LTR, splice acceptor, Bryan-RSV pol, subgroup A

Copyright information

© Humana Press Inc. 2007

Authors and Affiliations

  • Charlotta Lindvall
    • 1
  • Wen Bu
    • 2
  • Bart O. Williams
    • 1
  • Yi Li
    • 2
    • 3
  1. 1.Laboratory of Cell Signaling and CarcinogenesisVan Andel Research InstituteGrand RapidsUSA
  2. 2.Breast Center Baylor College of MedicineHoustonUSA
  3. 3.Department of Molecular and Cellular BiologyBaylor College of MedicineHoustonUSA