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

Gray W. Pearson, Tony Hunter

Research output: Contribution to journalArticle

45 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1555-1567
Number of pages13
JournalJournal of Cell Biology
Volume179
Issue number7
DOIs
StatePublished - Dec 31 2007

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ASJC Scopus subject areas

  • Cell Biology

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