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

E Reichmann, H Schwarz, EM Deiner, I Leitner… - Cell, 1992 - cell.com
E Reichmann, H Schwarz, EM Deiner, I Leitner, M Eilers, J Berger, M Busslinger, H Beug
Cell, 1992cell.com
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 …
Summary
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.
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