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

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast / metabolism
  • Breast / pathology
  • Breast / physiopathology*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Breast Neoplasms / physiopathology*
  • Cadherins / metabolism
  • Carcinoma / metabolism
  • Carcinoma / pathology
  • Carcinoma / physiopathology*
  • Cardiac Myosins / metabolism
  • Cell Adhesion
  • Cell Line
  • Cell Line, Tumor
  • Cell Movement*
  • Enzyme Activation / drug effects
  • Epithelial Cells / metabolism*
  • Epithelial Cells / pathology
  • Female
  • Humans
  • Mitogen-Activated Protein Kinase 3 / drug effects
  • Mitogen-Activated Protein Kinase 3 / metabolism*
  • Myosin Light Chains / metabolism
  • Myosin-Light-Chain Kinase / metabolism
  • Neoplasm Invasiveness / pathology
  • Neoplasm Invasiveness / physiopathology
  • Organ Culture Techniques
  • Phosphorylation
  • rho-Associated Kinases / metabolism

Substances

  • Cadherins
  • Myosin Light Chains
  • myosin light chain 2
  • rho-Associated Kinases
  • Myosin-Light-Chain Kinase
  • Mitogen-Activated Protein Kinase 3
  • Cardiac Myosins