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Time-lapse Imaging of Primary Preneoplastic Mammary Epithelial Cells Derived from Genetically Engineered Mouse Models of Breast Cancer
Published on: February 8, 2013
Stem/progenitor cells in mouse mammary gland development and breast cancer
1Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
Abstract:
Breast cancer is a genetically and clinically heterogeneous disease. It is unclear whether different target cells contribute to this heterogeneity and which cell types are most susceptible to oncogenesis. Stem cells are speculated to be the cellular origin of at least a subset of human breast cancers. To begin to address these issues, we have isolated and characterized cell populations enriched in normal mammary stem/progenitors and have studied the expression of putative stem/progenitor markers in tumors derived from genetically engineered mice. Specifically, transgenic activation of Wnt signaling in the mammary gland induces tumors comprised of epithelial and myoepithelial cells harboring the same genetic defect implying that the tumor arose from transformation of a bipotent progenitor cell. On the other hand, transgenic activation of Neu signaling induces tumors comprising cells of more limited lineage capacity. Thus, the heterogeneity of different breast cancers may reflect the activation of different oncogenic pathways, different cellular targets in which these genetic changes occur, or both.
Insights
Breast cancer heterogeneity may stem from different cell types initiating tumors. Mammary stem cells could be origins, with specific oncogenic pathways influencing tumor cell lineage capacity.
Area of Science:
- Oncology
- Stem Cell Biology
- Genetics
Background:
- Breast cancer exhibits significant genetic and clinical heterogeneity.
- The specific cell types contributing to this heterogeneity and their susceptibility to oncogenesis remain unclear.
- Mammary stem cells are hypothesized as potential origins for a subset of breast cancers.
Purpose of the Study:
- To investigate the role of mammary stem/progenitor cells in breast cancer heterogeneity.
- To characterize cell populations enriched in normal mammary stem/progenitors.
- To analyze the expression of stem/progenitor markers in mouse-derived tumors.
Main Methods:
- Isolation and characterization of normal mammary stem/progenitor cell populations.
- Generation of genetically engineered mouse models with specific oncogenic pathway activation (Wnt and Neu signaling).
- Analysis of tumor cell populations for epithelial and myoepithelial cell markers and lineage capacity.
Main Results:
- Transgenic Wnt signaling activation induced tumors from bipotent progenitor cells, affecting both epithelial and myoepithelial lineages.
- Transgenic Neu signaling activation resulted in tumors with more restricted cellular lineage capacity.
- Tumors derived from genetically engineered mice showed varying cellular compositions based on the activated oncogenic pathway.
Conclusions:
- Breast cancer heterogeneity can arise from the transformation of different progenitor cell types.
- The specific oncogenic pathway activated influences the cellular origin and lineage capacity of breast cancer tumors.
- Understanding the cellular targets of oncogenesis is crucial for deciphering breast cancer heterogeneity.
