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Découverte de nouveaux gènes cibles potentiels dans le génome humain pour les PPAR dans le domaine des interactions cellulaires

Abstract : New PPAR (Peoxisome Proliferator-Activated Receptors) target genes have been searched using two complementary protocols : immunoselection of human genomic DNA fragments that specifically bind PPARs and microarray. The first experimental approach has allowed the identification of a PPAR binding sequence located upstream the (HSA)SEMA6B gene. The latter encodes the semaphoring 6B, a protein involved in axonal interactions (Genomics, 2004, 83 : 1141-1150). From 13 human tumoral cell lines, we selected the MCF-7 breast adenocarcinoma, HepG2 hepatoblastoma and T98-G glioblastoma cell lines to study the impact of PPAR agonists, alone or in combination with the 9-cis-retinoic acid (a RXR agonist), on the expression of the (HSA)SEMA6B gene. A down regulation of this expression was noted whatever the activated PPAR isotype and the cell line investigated (Int. J. Oncol, 2006, 28:977-984). The repression has been observed at the transcriptional and translational levels. The latter was examined using an anti-semaphorin 6B polyclonal antibody that we have produced and characterized. On the other hand, an up-regulation of the (HSA)SEMA6B gene expression was obtained when the three cell lines were treated with thyroxin. Microarray analyses confirmed the down-regulation of the PPAR-induced (HSA)SEMA6B) gene expression. They revealed that thed expression of some genes involved in cellular interactions is modulated by PPARalpha and PPAR/delta.
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http://docnum.univ-lorraine.fr/prive/SCD_T_2006_0021_MURAD.pdf
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Submitted on : Thursday, March 29, 2018 - 10:41:30 AM
Last modification on : Thursday, May 28, 2020 - 10:35:09 AM

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Hossam Murad. Découverte de nouveaux gènes cibles potentiels dans le génome humain pour les PPAR dans le domaine des interactions cellulaires. Biologie moléculaire. Université Henri Poincaré - Nancy 1, 2006. Français. ⟨NNT : 2006NAN10021⟩. ⟨tel-01746626⟩

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