Activation of an inducible c-FosER fusion protein causes loss of epithelial polarity and triggers epithelial-fibroblastoid cell conversion.
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.
Reichmann
E
E
Forschungsinstitut für Molekulare Pathologie, Wien, Austria.
Schwarz
H
H
Deiner
E M
EM
Leitner
I
I
Eilers
M
M
Berger
J
J
Busslinger
M
M
Beug
H
H
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D016764:Cell Polarity / Q000187:drug effects; D004847:Epithelial Cells; D004967:Estrogens / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology; D008321:Mammary Glands, Animal / Q000166:cytology; D051379:Mice; D010641:Phenotype; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D011960:Receptors, Estrogen / Q000096:biosynthesis*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis*
D004967:Estrogens; D016760:Proto-Oncogene Proteins c-fos; D011960:Receptors, Estrogen; D011993:Recombinant Fusion Proteins