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Communication dans un congrès

Is TR alpha an oncogene ? Overexpression of P43 induces human dermal fibroblast transformation

Abstract : We have previously discovered p43, a truncated form of theTR alpha 1 nuclear receptor synthesized through the use of an internal AUG codon located in the TR alpha 1 transcript. P43 is a T3-dependent mitochondrial transcription factor leading to a stimulation of the organelle activity. We stably overexpressed p43 in human dermal fibroblasts. In parallel to a strong stimulation of mitochondrial activity correlated to an increase in ROS production, p43 overexpression induced strong morphological changes and cell fusion in myotubes-like structures associated with the expression of several muscle-specific genes (Myf5, desmin, connectin, myosin, AchR alpha). In addition, these cells displayed all the in vivo and in vitro features of cell transformation. This phenotype, very similar to that observed for rhabdomyosarcomas, was related to an increase in c-Jun, c-Fos and ATF2 expression, and extinction of tumor suppressor gene expression (p53, p21, Rb). Using chloramphenicol, an inhibitor of mitochondrial activity, we established the direct involvement of the stimulation of mitochondrial activity in this cell behaviour. Similar results were obtained using N-acetylcysteine, an inhibitor of ROS production. Lastly we also found that DNA hypermethylation was probably involved in the induction of this particular phenotype. All these data suggest that deregulation of p43 expression could lead to cell transformation through stimulation of mitochondrial activity, ROS production, and robably DNA methylation. They bring the first direct evidence that the TR alpha gene could be an actual oncogene, but quite unexpectedly through expression of the p43 mitochondrial T3 receptor.
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Communication dans un congrès
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https://hal.inrae.fr/hal-02818331
Déposant : Migration Prodinra <>
Soumis le : samedi 6 juin 2020 - 15:38:17
Dernière modification le : vendredi 12 juin 2020 - 10:43:26

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  • HAL Id : hal-02818331, version 1
  • PRODINRA : 9834

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Chantal Wrutniak-Cabello, S. Grandemange, P. Seyer, Francois Casas, Gerard Cabello. Is TR alpha an oncogene ? Overexpression of P43 induces human dermal fibroblast transformation. 31. Annual Meeting of the European Thyroid Association, Sep 2006, Naples, Italy. 1 p. ⟨hal-02818331⟩

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