Journal article
Hypoxia Suppression of Bim and Bmf Blocks Anoikis and Luminal Clearing during Mammary Morphogenesis
Molecular biology of the cell, v 21(22), pp 3829-3837
15 Nov 2010
PMID: 20861305
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Proper adhesion to extracellular matrix is critical for epithelial cell survival. Detachment from matrix signals results in apoptosis, referred to as anoikis. Selective apoptosis of cells that become detached from matrix is associated with the formation of a lumen in three-dimensional mammary epithelial acinar structures in vitro. Because early breast cancer lesions such as carcinoma in situ, characterized by ducts exhibiting lumens filled with cells, are often associated with hypoxic markers, we sought to examine the role of hypoxia in anoikis and lumen formation in mammary epithelial cells. Here, we show that hypoxic conditions inhibit anoikis and block expression of proapoptotic BH3-only family members Bim and Bmf in epithelial cells. Hypoxia-mediated anoikis protection is associated with increased activation of the epidermal growth factor receptor–mitogen-activated protein kinase kinase–extracellular signal-regulated kinase (Erk) kinase pathway and requires the hypoxia-activated transcription factor. Consistent with these data, hypoxic conditions inhibit luminal clearing during morphogenesis in human mammary epithelial acini when grown in three-dimensional cultures and are associated with decreased expression of Bim and Bmf as well as Erk activation. We show that hypoxia regulates specific cell survival pathways that disrupt tissue architecture related to clearing of luminal space during mammary morphogenesis and suggest that hypoxia-mediated anoikis resistance may contribute to cancer progression.
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Details
- Title
- Hypoxia Suppression of Bim and Bmf Blocks Anoikis and Luminal Clearing during Mammary Morphogenesis
- Creators
- Kelly A Whelan - Departments of Biochemistry and Molecular Biology andSarah A Caldwell - Departments of Biochemistry and Molecular Biology andKristina S Shahriari - Departments of Biochemistry and Molecular Biology andS. RaElle Jackson - Departments of Biochemistry and Molecular Biology andLisa D Franchetti - Pathology, Drexel University College of Medicine, Philadelphia, PA 19102Gregg J Johannes - Pathology, Drexel University College of Medicine, Philadelphia, PA 19102Mauricio J Reginato - Departments of Biochemistry and Molecular Biology and
- Contributors
- Keith E Mostov (Editor)
- Publication Details
- Molecular biology of the cell, v 21(22), pp 3829-3837
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology
- Web of Science ID
- WOS:000284216800035
- Scopus ID
- 2-s2.0-78649670285
- Other Identifier
- 991014877880504721
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- Web of Science research areas
- Cell Biology