Journal article
Bim Regulation of Lumen Formation in Cultured Mammary Epithelial Acini Is Targeted by Oncogenes
Molecular and cellular biology, v 25(11), pp 4591-4601
Jun 2005
PMID: 15899862
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Epithelial cells organize into cyst-like structures that contain a spherical monolayer of cells that enclose a central lumen. Using a three-dimensional basement membrane culture model in which mammary epithelial cells form hollow, acinus-like structures, we previously demonstrated that lumen formation is achieved, in part, through apoptosis of centrally localized cells. We demonstrate that the proapoptotic protein Bim may selectively trigger apoptosis of the centrally localized acinar cells, leading to temporally controlled lumen formation. Bim is not detectable during early stages of three-dimensional mammary acinar morphogenesis and is then highly upregulated in all cells of acini, coincident with detection of apoptosis in the centrally localized acinar cells. Inhibition of Bim expression by RNA interference transiently blocks luminal apoptosis and delays lumen formation. Oncogenes that induce acinar luminal filling, such as ErbB2 and v-Src, suppress expression of Bim through a pathway dependent on Erk-mitogen-activated protein kinase; however, HPV 16 E7, an oncogene that stimulates cell proliferation but not luminal filling, is unable to reduce Bim expression. Thus, Bim is a critical regulator of luminal apoptosis during mammary acinar morphogenesis in vitro and may be an important target of oncogenes that disrupt glandular epithelial architecture.
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Details
- Title
- Bim Regulation of Lumen Formation in Cultured Mammary Epithelial Acini Is Targeted by Oncogenes
- Creators
- Mauricio J Reginato - Department of Cell BiologyKenna R Mills - Department of Cell BiologyEsther B. E Becker - Department of Cell BiologyDanielle K Lynch - Department of Cell BiologyAzad Bonni - Department of Cell BiologySenthil K Muthuswamy - Department of Cell BiologyJoan S Brugge - Department of Cell Biology
- Publication Details
- Molecular and cellular biology, v 25(11), pp 4591-4601
- Publisher
- American Society for Microbiology
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology
- Web of Science ID
- WOS:000229275000023
- Scopus ID
- 2-s2.0-18944395927
- Other Identifier
- 991014877709004721
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- Web of Science research areas
- Biochemistry & Molecular Biology
- Cell Biology