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Etude du facteur de transcription précoce EGR1 dans l'effet antiprolifératif des ligands de PPAR[gamma] sur les cellules cancéreuses mammaires

Abstract : The ligands of PPAR[gamma] nuclear receptors (15-deoxy-[delta]12,14-Prostaglandin J2 (15d-PGJ2) and thiazolidinediones (TZDs) : troglitazone (TGZ), ciglitazone (CGZ)) show antiproliferative effects on breast cancer cell lines. Several studies suggest that the anti-cancer effects are PPAR[gamma]-independent. Our work is focused on the comprehension of such mechanisms of action. Our study has shown the induction of the transcription factor EGR1 (Early Growth Response gene 1) by some PPAR[gamma] ligands (TGZ, CGZ, 15d-PGJ2, and [delta]2-TGZ (PPAR[gamma] inactive agonist)) in the hormone-dependent breast cancer cells MCF7. This early effect is PPAR[gamma]-independent. It is associated with the almost immediate release of intracellular calcium followed by the activation of ERK1/2. EGR1 induction also occurs in the hormone-independent breast cancer cells MDA-MB-231 treated with [delta]2-TGZ. However, EGR1 induction plays only a partial role in the antiproliferative effect. Data analysis of DNA array has suggested the induction of an endoplasmic reticulum stress (ER) in MCF7 cells treated with [delta]2-TGZ. Complementary data have confirmed this result in MCF7 cells and in MDA-MB-231 cells. However, the role of ER stress in the antiproliferative effect is still to be determined. Finally, we have tested the hypothesis of a link between EGR1 and ER stress. Indeed, EGR1 is also early induced by other ER stress inductors. Diverse conditions where EGR1 is inhibited suggest a possible regulation of ATF3 expression by EGR1
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http://docnum.univ-lorraine.fr/prive/SCD_T_2011_0039_CHBICHEB.pdf
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https://hal.univ-lorraine.fr/tel-01746172
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Submitted on : Thursday, March 29, 2018 - 10:25:57 AM
Last modification on : Thursday, March 5, 2020 - 3:26:56 PM

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  • HAL Id : tel-01746172, version 1

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Sarra Chbicheb. Etude du facteur de transcription précoce EGR1 dans l'effet antiprolifératif des ligands de PPAR[gamma] sur les cellules cancéreuses mammaires. Médecine humaine et pathologie. Université Henri Poincaré - Nancy 1, 2011. Français. ⟨NNT : 2011NAN10039⟩. ⟨tel-01746172⟩

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