Activation of an inducible c-FosER fusion protein causes loss of epithelial polarity and triggers epithelial-fibroblastoid cell conversion

Cell. 1992 Dec 24;71(7):1103-16. doi: 10.1016/s0092-8674(05)80060-1.

Abstract

As a novel approach to studying the modulation of the polarized epithelial phenotype, we have expressed c-Fos and c-Myc estrogen receptor fusion proteins (c-FosER and c-MycER) in mammary epithelial cells. The hybrid proteins could be activated by estrogen for defined time periods and after the cells had achieved their fully polarized organization. Activation of c-MycER deregulated proliferation but did not affect epithelial polarity. Short-term activation of c-FosER induced the reversible loss of morphological and functional cell polarity. In contrast, long-term stimulation of c-FosER caused the cells to depolarize irreversibly, to invade collagen gels, and to undergo epithelial-fibroblastoid cell conversion. Our data suggest that Fos proteins are important in modulating the epithelial phenotype both in normal tissue development and in invasive processes.

MeSH terms

  • Animals
  • Cell Differentiation / drug effects
  • Cell Division / drug effects
  • Cell Line
  • Cell Polarity* / drug effects
  • Epithelial Cells
  • Estrogens / pharmacology
  • Fibroblasts / cytology
  • Mammary Glands, Animal / cytology
  • Mice
  • Phenotype
  • Proto-Oncogene Proteins c-fos / biosynthesis*
  • Receptors, Estrogen / biosynthesis*
  • Recombinant Fusion Proteins / biosynthesis*

Substances

  • Estrogens
  • Proto-Oncogene Proteins c-fos
  • Receptors, Estrogen
  • Recombinant Fusion Proteins