Role of epithelial to mesenchymal transition associated genes in mammary gland regeneration and breast tumorigenesis
| Autor: | Neethan A. Lobo, Sopheak Sim, Tomer Kalisky, Shang Cai, George Somlo, Dalong Qian, Angera H. Kuo, Shaheen S. Sikandar, Michael F. Clarke, Stephen R. Quake, Ferenc A. Scheeren, Frederick M. Dirbas, Maider Zabala, Robert W. Hsieh |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Epithelial-Mesenchymal Transition Science Transplantation Heterologous General Physics and Astronomy Mice Transgenic Triple Negative Breast Neoplasms Mice SCID Biology medicine.disease_cause General Biochemistry Genetics and Molecular Biology Article Metastasis 03 medical and health sciences Breast cancer Mice Inbred NOD medicine Animals Humans Regeneration Epithelial–mesenchymal transition Breast skin and connective tissue diseases lcsh:Science Triple-negative breast cancer Mice Knockout Multidisciplinary Gene Expression Profiling Mesenchymal stem cell Cancer Epithelial Cells General Chemistry medicine.disease 3. Good health Mice Inbred C57BL 030104 developmental biology Cell Transformation Neoplastic Cancer research Female lcsh:Q Stem cell Carcinogenesis Interleukin Receptor Common gamma Subunit |
| Zdroj: | Nature Communications, Vol 8, Iss 1, Pp 1-9 (2017) Nature Communications, 8 Nature Communications |
| Popis: | Previous studies have proposed that epithelial to mesenchymal transition (EMT) in breast cancer cells regulates metastasis, stem cell properties and chemo-resistance; most studies were based on in vitro culture of cell lines and mouse transgenic cancer models. However, the identity and function of cells expressing EMT-associated genes in normal murine mammary gland homeostasis and human breast cancer still remains under debate. Using in vivo lineage tracing and triple negative breast cancer (TNBC) patient derived xenografts we demonstrate that the repopulating capacity in normal mammary epithelial cells and tumorigenic capacity in TNBC is independent of expression of EMT-associated genes. In breast cancer, while a subset of cells with epithelial and mesenchymal phenotypes have stem cell activity, in many cells that have lost epithelial characteristics with increased expression of mesenchymal genes, have decreased tumor-initiating capacity and plasticity. These findings have implications for the development of effective therapeutic agents targeting tumor-initiating cells. The contribution of EMT in mammary gland homeostasis and human breast cancer is still unclear. Here, using in vivo lineage tracing and breast cancer PDXs the authors demonstrate that the repopulating capacity in normal mammary epithelial cells and tumorigenic capacity in breast cancer is independent of expression of EMT-associated genes. |
| Databáze: | OpenAIRE |
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