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PMID: 17873348 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Review

Wnt signaling, stem cells, and the cellular origin of breast cancer.

Stem cell reviews ·Vol. 3 ·No. 2 ·2007-06-00 ·Pages 157-68

Lindvall C, Bu W, Williams BO, Li Y

Abstract

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 beta-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.

MeSH Terms
Animals Antigens, Polyomavirus Transforming/metabolism Biomarkers, Tumor/metabolism Breast Neoplasms/metabolism,pathology Cell Differentiation Cell Transformation, Neoplastic Epithelial Cells/metabolism,pathology Female Humans LDL-Receptor Related Proteins/metabolism Low Density Lipoprotein Receptor-Related Protein-5 Low Density Lipoprotein Receptor-Related Protein-6 Mammary Glands, Animal/metabolism,pathology Mammary Glands, Human/metabolism,pathology Mammary Neoplasms, Animal/metabolism,pathology Neoplastic Stem Cells/metabolism,pathology Protein Kinases/metabolism Signal Transduction TOR Serine-Threonine Kinases Wnt Proteins/metabolism beta Catenin/metabolism
Chemicals
Antigens, Polyomavirus Transforming Biomarkers, Tumor LDL-Receptor Related Proteins LRP5 protein, human LRP6 protein, human Low Density Lipoprotein Receptor-Related Protein-5 Low Density Lipoprotein Receptor-Related Protein-6 Wnt Proteins beta Catenin Protein Kinases MTOR protein, human TOR Serine-Threonine Kinases
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Lindvall Charlotta
Laboratory of Cell Signaling and Carcinogenesis, Van Andel Research Institute, 333 Bostwick NE, Grand Rapids, MI 49503, USA.
Bu Wen
Williams Bart O
Li Yi
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Article Info
Journal
Stem cell reviews
Abbr.
Stem Cell Rev
ISSN
1550-8943
DOI
10.1007/s12015-007-0025-3
Published
2007-06-00
Pages
157-68
Language
English
Region
United States
NLM ID
101255952
Subset
IM
Grants
NCI NIH HHS · R01 CA113869 · United States
NCI NIH HHS · U01 CA084243-07 · United States
External Links
PubMed source DOI: 10.1007/s12015-007-0025-3 View journal details
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