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Etude comparative de récepteurs aux œstrogènes : Aspects moléculaire et cellulaire de la réponse aux œstrogènes et anti-œstrogènes impliqués dans les causes et thérapies du cancer du sein.

Abstract : Estrogens (E2), through estrogen receptors (ERs), control the expression of a number of genes involved in growth, cellular differentiation and reproductive functions. Regulation of these genes is carried out by the ER binding to a DNA sequence: the Estrogen Responsive Element (ERE). ERs play a major role in breast cancer and therefore it's important to understand the molecular mechanisms which modulate ER activity in vivo. We found that, compared to the consensus ERE, ERs exhibit a lesser affinity for the imperfect ERE (rtvtgERE), cellular activity and E2 sensitivity. An in vitro study on the ERs conformational, thermodynamical and dynamical behaviour has proved that the electrostatic network plays a role in their different functionalities. We researched and compared the impact of the ligands fixation on the cellular activity of two ER: hERalpha and rtERS. The transcriptional mechanism created in yeast allowed us to show that hERalpha is a transcriptional activator which is more potent and more sensitive to E2 than rtERS. We observed that the presence of the ligand induces ER localization within foci. Time curses of the ER transcriptional activation and sub-cellular localization in the presence of ligands lead us to distinguish these two aspects. We suggest that a high phosphorylation level by kinases activated in the presence of ligand increases the ER anionic character tending either to prevent the fixation on the DNA or to increase their dissociation from the DNA. Thus, ERs could be recruited by complexes in the nucleus or cytoplasm and form some foci.
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https://tel.archives-ouvertes.fr/tel-00470517
Contributor : Adélaïde Le Grand <>
Submitted on : Tuesday, April 6, 2010 - 5:28:49 PM
Last modification on : Wednesday, October 14, 2020 - 4:09:38 AM
Long-term archiving on: : Tuesday, September 14, 2010 - 5:04:45 PM

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  • HAL Id : tel-00470517, version 1

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Adélaïde Le Grand. Etude comparative de récepteurs aux œstrogènes : Aspects moléculaire et cellulaire de la réponse aux œstrogènes et anti-œstrogènes impliqués dans les causes et thérapies du cancer du sein.. Biochimie [q-bio.BM]. Université de Bretagne Sud, 2009. Français. ⟨tel-00470517⟩

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