Different Outcomes of Unliganded and Liganded Estrogen Receptor-α on Neurite Outgrowth in PC12 Cells
| Autor: | François Ferrière, Luc Gailhouste, Gilles Flouriot, Yohann Mérot, Frédéric Percevault, Christian Saligaut, Guillaume Huet |
|---|---|
| Přispěvatelé: | Interactions cellulaires et moléculaires (ICM), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 2008 |
| Předmět: |
MAPK/ERK pathway
medicine.medical_specialty Transcription Genetic Neurite Estrogen receptor [SDV.CAN]Life Sciences [q-bio]/Cancer Biology Ligands PC12 Cells Phosphatidylinositol 3-Kinases 03 medical and health sciences Transactivation 0302 clinical medicine Endocrinology Internal medicine Neurites medicine Animals [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology Nerve Growth Factors Extracellular Signal-Regulated MAP Kinases 10. No inequality Diethylstilbestrol Psychological repression Protein kinase B 030304 developmental biology [SDV.EE.SANT]Life Sciences [q-bio]/Ecology environment/Health 0303 health sciences Estrogen Receptor alpha Gene Amplification Genetic Variation Clone Cells Rats Nerve growth factor Signal transduction hormones hormone substitutes and hormone antagonists Cell Division 030217 neurology & neurosurgery |
| Zdroj: | Endocrinology Endocrinology, 2009, 150 (1), pp.200-11. ⟨10.1210/en.2008-0449⟩ Endocrinology, Endocrine Society, 2009, 150 (1), pp.200-11. ⟨10.1210/en.2008-0449⟩ |
| ISSN: | 1945-7170 0013-7227 |
| DOI: | 10.1210/en.2008-0449 |
| Popis: | A precise description of the mechanisms by which estrogen receptor-α (ERα) exerts its influences on cellular growth and differentiation is still pending. Here, we report that the differentiation of PC12 cells is profoundly affected by ERα. Importantly, depending upon its binding to 17β-estradiol (17βE2), ERα is found to exert different effects on pathways involved in nerve growth factor (NGF) signaling. Indeed, upon its stable expression in PC12 cells, unliganded ERα is able to partially inhibit the neurite outgrowth induced by NGF. This process involves a repression of MAPK and phosphatidylinositol 3-kinase/Akt signaling pathways, which leads to a negative regulation of markers of neuronal differentiation such as VGF and NFLc. This repressive action of unliganded ERα is mediated by its D domain and does not involve its transactivation and DNA-binding domains, thereby suggesting that direct transcriptional activity of ERα is not required. In contrast with this repressive action occurring in the absence of 17βE2, the expression of ERα in PC12 cells allows 17βE2 to potentiate the NGF-induced neurite outgrowth. Importantly, 17βE2 has no impact on NGF-induced activity of MAPK and Akt signaling pathways. The mechanisms engaged by liganded ERα are thus unlikely to rely on an antagonism of the inhibition mediated by the unliganded ERα. Furthermore, 17βE2 enhances NGF-induced response of VGF and NFLc neuronal markers in PC12 clones expressing ERα. This stimulatory effect of 17βE2 requires the transactivation functions of ERα and its D domain, suggesting that an estrogen-responsive element-independent transcriptional mechanism is potentially relevant for the neuritogenic properties of 17βE2 in ERα-expressing PC12 cells.In the absence of its ligand, ERα partially inhibits the nerve growth factor-induced neurite outgrowth of PC12 cells, whereas, once liganded, it enhances differentiation. |
| Databáze: | OpenAIRE |
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