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Surviving without oxygen: hypoxia regulation of mammary morphogenesis and anoikis
Journal article   Open access   Peer reviewed

Surviving without oxygen: hypoxia regulation of mammary morphogenesis and anoikis

Kelly A Whelan and Mauricio J Reginato
Cell cycle (Georgetown, Tex.), v 10(14), pp 2287-2294
15 Jul 2011
DOI: https://doi.org/10.4161/cc.10.14.16532
PMID: 21670595
Featured in Collection :   UN Sustainable Development Goals @ Drexel
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https://doi.org/10.4161/cc.10.14.16532View
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Abstract

Proto-Oncogene Proteins - metabolism Mammary Glands, Human - cytology Epithelial Cells - metabolism Signal Transduction Humans Extracellular Signal-Regulated MAP Kinases - metabolism Oxygen - metabolism Apoptosis Regulatory Proteins - metabolism Breast Neoplasms - metabolism Cell Hypoxia Bcl-2-Like Protein 11 Breast Neoplasms - pathology Hypoxia-Inducible Factor 1, alpha Subunit - metabolism Anoikis Female Membrane Proteins - metabolism Epithelial Cells - cytology
Tumor hypoxia correlates with resistance to chemotherapy, increased incidence of metastasis and poor clinical prognosis. Early breast cancer lesions, such as carcinoma in situ, characterized by filled lumens, are often associated with hypoxic markers. However, the contribution of hypoxia to changes in tissue architecture in early pre-malignant lesions is not well defined. Using three-dimensional basement membrane cultures of mammary epithelial cells, we recently reported that acini-like structures exposed to hypoxia display epithelial disorganization and delayed lumen formation. We found that hypoxia, via HIF-1α, targets signaling pathways, specifically the Erk-Bim axis, to suppress anoikis-cell death in a 3D acinar model. Here, we discuss these findings further and present additional data, indicating that hypoxia-mediated alterations in acinar architecture and anoikis-associated Erk-Bim signaling are maintained in mammary epithelial cells after reoxygenation. Taken together, these findings may offer new insight into the contribution of hypoxia-mediated signaling in the progression of early breast cancer lesions and possible treatment of hypoxic cancers.

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Cell Biology
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