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J Cell Biol. 2007 Dec 31;179(7):1555-67. doi: 10.1083/jcb.200706099.

Real-time imaging reveals that noninvasive mammary epithelial acini can contain motile cells.

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  • 1Molecular and Cell Biology Laboratory, Salk Institute, La Jolla, CA 92037, USA.

Abstract

To determine how extracellular signal-regulated kinases (ERK) 1/2 promote mammary tumorigenesis, we examined the real-time behavior of cells in an organotypic culture of the mammary glandular epithelium. Inducible activation of ERK1/2 in mature acini elicits cell motility and disrupts epithelial architecture in a manner that is reminiscent of ductal carcinoma in situ; however, motile cells do not invade through the basement membrane and branching morphogenesis does not take place. ERK1/2-induced motility causes cells to move both within the cell monolayer that contacts the basement membrane surrounding the acinus and through the luminal space of the acinus. E-cadherin expression is reduced after ERK1/2 activation, but motility does not involve an epithelial-mesenchymal transition. Cell motility and the disruption of epithelial architecture require a Rho kinase- and myosin light chain kinase-dependent increase in the phosphorylation of myosin light chain 2. Our results identify a new mechanism for the disruption of architecture in epithelial acini and suggest that ERK1/2 can promote noninvasive motility in preinvasive mammary tumors.

PMID:
18166657
[PubMed - indexed for MEDLINE]
PMCID:
PMC2373504
Free PMC Article
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