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

Citation
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
Citations number
39
Categorie Soggetti
Developmental Biology","Cell Biology
Journal title
ISSN journal
03014681
Volume
60
Issue
4
Year of publication
1996
Pages
211 - 218
Database
ISI
SICI code
0301-4681(1996)60:4<211:MEFCDF>2.0.ZU;2-D
Abstract
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.