Reactive oxygen species initiate luminal but not basal cell death in cultured human mammary alveolar structures: A potential regulator of involution
Post-lactational involution of the mammary gland is initiated within days of weaning. Clearing of cells occurs by apoptosis of the milk-secreting luminal cells in the alveoli and through stromal tissue remodeling to return the gland almost completely to its pre-pregnant state. The pathways that spec...
| Main Authors: | , , , |
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| Format: | Journal Article |
| Published: |
2011
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| Online Access: | http://hdl.handle.net/20.500.11937/4535 |
| _version_ | 1848744543387648000 |
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| author | Thomas, E. Zeps, Nikolajs Rigby, P. Hartmann, P. |
| author_facet | Thomas, E. Zeps, Nikolajs Rigby, P. Hartmann, P. |
| author_sort | Thomas, E. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | Post-lactational involution of the mammary gland is initiated within days of weaning. Clearing of cells occurs by apoptosis of the milk-secreting luminal cells in the alveoli and through stromal tissue remodeling to return the gland almost completely to its pre-pregnant state. The pathways that specifically target involution of the luminal cells in the alveoli but not the basal and ductal cells are poorly understood. In this study we show in cultured human mammary alveolar structures that the involution process is initiated by fresh media withdrawal, and is characterized by cellular oxidative stress, expression of activated macrophage marker CD68 and finally complete clearing of the luminal but not basal epithelial layer. This process can be simulated by ectopic addition of reactive oxygen species (ROS) in cultures without media withdrawal. Cells isolated from post-involution alveoli were enriched for the CD49f(+) mammary stem cell (MaSC) phenotype and were able to reproduce a complete alveolar structure in subcultures without any significant loss in viability. We propose that the ROS produced by accumulated milk breakdown post-weaning may be the mechanism underlying the selective involution of secretory alveolar luminal cells, and that our culture model represents an useful means to investigate this and other mechanisms further. |
| first_indexed | 2025-11-14T06:03:08Z |
| format | Journal Article |
| id | curtin-20.500.11937-4535 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T06:03:08Z |
| publishDate | 2011 |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-45352017-09-13T14:39:15Z Reactive oxygen species initiate luminal but not basal cell death in cultured human mammary alveolar structures: A potential regulator of involution Thomas, E. Zeps, Nikolajs Rigby, P. Hartmann, P. Post-lactational involution of the mammary gland is initiated within days of weaning. Clearing of cells occurs by apoptosis of the milk-secreting luminal cells in the alveoli and through stromal tissue remodeling to return the gland almost completely to its pre-pregnant state. The pathways that specifically target involution of the luminal cells in the alveoli but not the basal and ductal cells are poorly understood. In this study we show in cultured human mammary alveolar structures that the involution process is initiated by fresh media withdrawal, and is characterized by cellular oxidative stress, expression of activated macrophage marker CD68 and finally complete clearing of the luminal but not basal epithelial layer. This process can be simulated by ectopic addition of reactive oxygen species (ROS) in cultures without media withdrawal. Cells isolated from post-involution alveoli were enriched for the CD49f(+) mammary stem cell (MaSC) phenotype and were able to reproduce a complete alveolar structure in subcultures without any significant loss in viability. We propose that the ROS produced by accumulated milk breakdown post-weaning may be the mechanism underlying the selective involution of secretory alveolar luminal cells, and that our culture model represents an useful means to investigate this and other mechanisms further. 2011 Journal Article http://hdl.handle.net/20.500.11937/4535 10.1038/cddis.2011.69 unknown |
| spellingShingle | Thomas, E. Zeps, Nikolajs Rigby, P. Hartmann, P. Reactive oxygen species initiate luminal but not basal cell death in cultured human mammary alveolar structures: A potential regulator of involution |
| title | Reactive oxygen species initiate luminal but not basal cell death in cultured human mammary alveolar structures: A potential regulator of involution |
| title_full | Reactive oxygen species initiate luminal but not basal cell death in cultured human mammary alveolar structures: A potential regulator of involution |
| title_fullStr | Reactive oxygen species initiate luminal but not basal cell death in cultured human mammary alveolar structures: A potential regulator of involution |
| title_full_unstemmed | Reactive oxygen species initiate luminal but not basal cell death in cultured human mammary alveolar structures: A potential regulator of involution |
| title_short | Reactive oxygen species initiate luminal but not basal cell death in cultured human mammary alveolar structures: A potential regulator of involution |
| title_sort | reactive oxygen species initiate luminal but not basal cell death in cultured human mammary alveolar structures: a potential regulator of involution |
| url | http://hdl.handle.net/20.500.11937/4535 |