Nuclear retinoic acid receptor characterization in cultured human trophoblast cells: effect of retinoic acid on epidermal growth factor receptor expression.
Vitamin A is an important factor during gestation and its metabolite, retinoic acid (RA), is a potent teratogen. However, RA action on the placenta is still poorly understood. In this study we analysed the presence of RARs and RXRs in human trophoblastic cells. We determined that RAR alpha was the more expressed form in term placenta, and that RAR beta was induced by RA treatment. Then we analysed RA effects on endocrine activities and on epidermal growth factor (EGF) receptor expression. We found that RA decreased 125I-labeled EGF binding and EGF-dependent phosphorylation. Furthermore, RA treatment led to a concentration-dependent decrease in the amount of EGFR protein expression. This treatment also decreased EGF receptor mRNA levels, suggesting transcriptional regulation of the EGF receptor. Thus we demonstrated that RA could interact with feto-placental development by modulating trophoblast EGF receptors expression, probably via its nuclear receptors.
Laboratoire de Physiopathologie du Développement, CNRS URA 1337, ENS, Paris, France.
S
S
Roulier
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Rochette-Egly
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C
Rebut-Bonneton
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Porquet
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D
Evain-Brion
D015152:Blotting, Northern; D002454:Cell Differentiation / Q000187:drug effects; D002467:Cell Nucleus / Q000737:chemistry / Q000648:ultrastructure; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000032:analysis* / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006801:Humans; D007457:Iodine Radioisotopes; D009687:Nuclear Proteins / Q000032:analysis / Q000187:drug effects / Q000235:genetics; D010920:Placenta / Q000737:chemistry / Q000166:cytology / Q000648:ultrastructure; D011247:Pregnancy; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D018168:Receptors, Retinoic Acid / Q000032:analysis* / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D047488:Retinoid X Receptors; D014157:Transcription Factors / Q000032:analysis / Q000187:drug effects / Q000235:genetics; D014158:Transcription, Genetic; D014212:Tretinoin / Q000633:toxicity*; D014327:Trophoblasts / Q000737:chemistry* / Q000166:cytology / Q000187:drug effects / Q000648:ultrastructure
D007457:Iodine Radioisotopes; D009687:Nuclear Proteins; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors; D014212:Tretinoin; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases