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Conditionally Reprogrammed Normal and Transformed Mouse Mammary Epithelial Cells Display a Progenitor-Cell–Like Phenotype
Mammary epithelial (ME) cells cultured under conventional conditions senesce after several passages. Here, we demonstrate that mouse ME cells isolated from normal mammary glands or from mouse mammary tumor virus (MMTV)-Neu–induced mammary tumors, can be cultured indefinitely as conditionally reprogr...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4022745/ https://www.ncbi.nlm.nih.gov/pubmed/24831228 http://dx.doi.org/10.1371/journal.pone.0097666 |
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author | Saenz, Francisco R. Ory, Virginie AlOtaiby, Maram Rosenfield, Sonia Furlong, Mary Cavalli, Luciane R. Johnson, Michael D. Liu, Xuefeng Schlegel, Richard Wellstein, Anton Riegel, Anna T. |
author_facet | Saenz, Francisco R. Ory, Virginie AlOtaiby, Maram Rosenfield, Sonia Furlong, Mary Cavalli, Luciane R. Johnson, Michael D. Liu, Xuefeng Schlegel, Richard Wellstein, Anton Riegel, Anna T. |
author_sort | Saenz, Francisco R. |
collection | PubMed |
description | Mammary epithelial (ME) cells cultured under conventional conditions senesce after several passages. Here, we demonstrate that mouse ME cells isolated from normal mammary glands or from mouse mammary tumor virus (MMTV)-Neu–induced mammary tumors, can be cultured indefinitely as conditionally reprogrammed cells (CRCs) on irradiated fibroblasts in the presence of the Rho kinase inhibitor Y-27632. Cell surface progenitor-associated markers are rapidly induced in normal mouse ME-CRCs relative to ME cells. However, the expression of certain mammary progenitor subpopulations, such as CD49f(+) ESA(+) CD44(+), drops significantly in later passages. Nevertheless, mouse ME-CRCs grown in a three-dimensional extracellular matrix gave rise to mammary acinar structures. ME-CRCs isolated from MMTV-Neu transgenic mouse mammary tumors express high levels of HER2/neu, as well as tumor-initiating cell markers, such as CD44(+), CD49f(+), and ESA(+) (EpCam). These patterns of expression are sustained in later CRC passages. Early and late passage ME-CRCs from MMTV-Neu tumors that were implanted in the mammary fat pads of syngeneic or nude mice developed vascular tumors that metastasized within 6 weeks of transplantation. Importantly, the histopathology of these tumors was indistinguishable from that of the parental tumors that develop in the MMTV-Neu mice. Application of the CRC system to mouse mammary epithelial cells provides an attractive model system to study the genetics and phenotype of normal and transformed mouse epithelium in a defined culture environment and in vivo transplant studies. |
format | Online Article Text |
id | pubmed-4022745 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-40227452014-05-21 Conditionally Reprogrammed Normal and Transformed Mouse Mammary Epithelial Cells Display a Progenitor-Cell–Like Phenotype Saenz, Francisco R. Ory, Virginie AlOtaiby, Maram Rosenfield, Sonia Furlong, Mary Cavalli, Luciane R. Johnson, Michael D. Liu, Xuefeng Schlegel, Richard Wellstein, Anton Riegel, Anna T. PLoS One Research Article Mammary epithelial (ME) cells cultured under conventional conditions senesce after several passages. Here, we demonstrate that mouse ME cells isolated from normal mammary glands or from mouse mammary tumor virus (MMTV)-Neu–induced mammary tumors, can be cultured indefinitely as conditionally reprogrammed cells (CRCs) on irradiated fibroblasts in the presence of the Rho kinase inhibitor Y-27632. Cell surface progenitor-associated markers are rapidly induced in normal mouse ME-CRCs relative to ME cells. However, the expression of certain mammary progenitor subpopulations, such as CD49f(+) ESA(+) CD44(+), drops significantly in later passages. Nevertheless, mouse ME-CRCs grown in a three-dimensional extracellular matrix gave rise to mammary acinar structures. ME-CRCs isolated from MMTV-Neu transgenic mouse mammary tumors express high levels of HER2/neu, as well as tumor-initiating cell markers, such as CD44(+), CD49f(+), and ESA(+) (EpCam). These patterns of expression are sustained in later CRC passages. Early and late passage ME-CRCs from MMTV-Neu tumors that were implanted in the mammary fat pads of syngeneic or nude mice developed vascular tumors that metastasized within 6 weeks of transplantation. Importantly, the histopathology of these tumors was indistinguishable from that of the parental tumors that develop in the MMTV-Neu mice. Application of the CRC system to mouse mammary epithelial cells provides an attractive model system to study the genetics and phenotype of normal and transformed mouse epithelium in a defined culture environment and in vivo transplant studies. Public Library of Science 2014-05-15 /pmc/articles/PMC4022745/ /pubmed/24831228 http://dx.doi.org/10.1371/journal.pone.0097666 Text en © 2014 Saenz et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Saenz, Francisco R. Ory, Virginie AlOtaiby, Maram Rosenfield, Sonia Furlong, Mary Cavalli, Luciane R. Johnson, Michael D. Liu, Xuefeng Schlegel, Richard Wellstein, Anton Riegel, Anna T. Conditionally Reprogrammed Normal and Transformed Mouse Mammary Epithelial Cells Display a Progenitor-Cell–Like Phenotype |
title | Conditionally Reprogrammed Normal and Transformed Mouse Mammary Epithelial Cells Display a Progenitor-Cell–Like Phenotype |
title_full | Conditionally Reprogrammed Normal and Transformed Mouse Mammary Epithelial Cells Display a Progenitor-Cell–Like Phenotype |
title_fullStr | Conditionally Reprogrammed Normal and Transformed Mouse Mammary Epithelial Cells Display a Progenitor-Cell–Like Phenotype |
title_full_unstemmed | Conditionally Reprogrammed Normal and Transformed Mouse Mammary Epithelial Cells Display a Progenitor-Cell–Like Phenotype |
title_short | Conditionally Reprogrammed Normal and Transformed Mouse Mammary Epithelial Cells Display a Progenitor-Cell–Like Phenotype |
title_sort | conditionally reprogrammed normal and transformed mouse mammary epithelial cells display a progenitor-cell–like phenotype |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4022745/ https://www.ncbi.nlm.nih.gov/pubmed/24831228 http://dx.doi.org/10.1371/journal.pone.0097666 |
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