MURINE ENDODERMAL F9E CELLS, DERIVED FROM THE TERATOCARCINOMA LINE F9, CONTAIN HIGH BASAL LEVELS OF RETINOIC ACID RECEPTORS (RARS AND RXRS)BUT ARE NOT SENSITIVE TO THE ACTIONS OF RETINOIC ACID
Yjy. Wan et al., MURINE ENDODERMAL F9E CELLS, DERIVED FROM THE TERATOCARCINOMA LINE F9, CONTAIN HIGH BASAL LEVELS OF RETINOIC ACID RECEPTORS (RARS AND RXRS)BUT ARE NOT SENSITIVE TO THE ACTIONS OF RETINOIC ACID, Differentiation, 60(4), 1996, pp. 211-218
Retinoic acid (RA)-induced endodermal differentiation of F9 teratocarc
inoma cells is accompanied by altered of many genes, including the ret
inoic acid receptor (RAR) alpha, beta, and gamma and retinoic x recept
or (RXR) alpha and gamma genes. In addition, RA enhances the binding o
f nuclear receptors to the RA responsive elements and increases the tr
ans-activation of the RA-responsive genes in F9 cells. These data sugg
est that RA increases the overall function of RA receptors in F9 cells
. However, the cell line F9E, established by long-term exposure of F9
cells to RA, is insensitive to RA. These cells expressed the genes for
keratin 8 and tissue specific plasminogen activator (t-PA), which are
characteristic of endoderm cells. Northern blot analysis showed that
F9E cells expressed high basal levels of RAR and RXR mRNAs, but genes
including the RARs and RXRs, which are normally regulated by RA in F9
cells, were no longer regulated in F9E cells. Further, F9E cells were
not sensitive to the antiproliferative effect of RA. In these cells, h
igh levels of RA receptors constitutively bound to RA responsive eleme
nts, but RA could neither increase the amount of RA receptor binding t
o the RA responsive elements, nor enhance the transcription of the RA
target genes. These findings provide a possible explanation for insens
itivity of endodermal cells to the actions of RA. Our data also indica
te that the levels of endogenous RA receptors do not predict the degre
e of RA sensitivity, and that RA responsiveness might be a function of
the cell's ability to regulate RA receptor genes.