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Activation of the mTOR/ Akt pathway in thymic epithelial cells derived from thymomas

Jean-Michel Maury, Claire Merveilleux du Vignaux, View ORCID ProfileGabrielle Drevet, Virginie Zarza, Lara chalabreysse, François Tronc, Nicolas Girard, View ORCID ProfileCaroline Leroux
doi: https://doi.org/10.1101/317297
Jean-Michel Maury
Groupement hospitalier Est, HCL;
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Claire Merveilleux du Vignaux
Groupement Hospitalier Est;
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Gabrielle Drevet
Groupement Hospitalier Est;
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Virginie Zarza
Groupement Hospitalier Est;
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Lara chalabreysse
Groupement Hospitalier Est;
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François Tronc
Groupement Hospitalier Est, HCL;
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Nicolas Girard
Institut du thorax Monsouris;
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Caroline Leroux
INRA
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  • ORCID record for Caroline Leroux
  • For correspondence: caroline.leroux@univ-lyon1.fr
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Abstract

The pathogenesis of thymic epithelial tumors remains poorly elucidated. The PI3K/Akt/mTOR pathway plays a key role in various cancers and among them thymic tumors; interestingly, several phase I/II study reported a positive effect of mTOR inhibitors in disease control. A major limit for deciphering cellular and molecular events leading to the transformation of thymic epithelial cells or for testing drug candidates is the lack of reliable in vitro cell system We analyzed protein expression and activation of key players of the Akt/mTOR pathway namely Akt, mTOR, and P70S6K in thirteen A, B and AB thymomas as well as in normal thymuses. While only Akt and the phospho- Akt were expressed in normal thymuses, both Akt and mTOR were activated, with B2 thymomas expressing higher level of activated phospho- Akt than A or AB subtypes. Phospho- P70S6K was expressed in all thymic tumors whatever their subtypes, and absent in normal thymus. Interestingly, in primary thymic epithelial cells maintained for short period of time after their derivation from seven AB and B thymomas, we report the activation of Akt; mTOR and P70S6. Finally, we analyzed the effect of mTOR inhibitor on thymoma derived epithelial cells and showed that rapamycin (100 nM/ ml) significantly reduced cell proliferation. Our results suggest that the activation of the Akt/ mTOR pathway might participate to the cell proliferation associated with tumor growth. Ultimately, our data enhance the potential role of thymic epithelial cells derived from tissue specimens for in vitro exploration of molecular abnormalities specific to rare thymic tumors.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted May 08, 2018.
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Activation of the mTOR/ Akt pathway in thymic epithelial cells derived from thymomas
Jean-Michel Maury, Claire Merveilleux du Vignaux, Gabrielle Drevet, Virginie Zarza, Lara chalabreysse, François Tronc, Nicolas Girard, Caroline Leroux
bioRxiv 317297; doi: https://doi.org/10.1101/317297
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Activation of the mTOR/ Akt pathway in thymic epithelial cells derived from thymomas
Jean-Michel Maury, Claire Merveilleux du Vignaux, Gabrielle Drevet, Virginie Zarza, Lara chalabreysse, François Tronc, Nicolas Girard, Caroline Leroux
bioRxiv 317297; doi: https://doi.org/10.1101/317297

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