Cargando…

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

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 arc...

Descripción completa

Detalles Bibliográficos
Autores principales: Pearson, Gray W., Hunter, Tony
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2373504/
https://www.ncbi.nlm.nih.gov/pubmed/18166657
http://dx.doi.org/10.1083/jcb.200706099
Descripción
Sumario: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.