Targeting the JNK Signaling Pathway Potentiates the Antiproliferative Efficacy of Rapamycin in LS174T Colon Cancer Cells.

Détails

ID Serval
serval:BIB_84ED06416D71
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Targeting the JNK Signaling Pathway Potentiates the Antiproliferative Efficacy of Rapamycin in LS174T Colon Cancer Cells.
Périodique
Journal of Surgical Research
Auteur(s)
Benoit M., Dormond-Meuwly A., Demartines N., Dormond O.
ISSN
1095-8673 (Electronic)
ISSN-L
0022-4804
Statut éditorial
Publié
Date de publication
2011
Volume
167
Numéro
2
Pages
e193-e198
Langue
anglais
Résumé
Background. Targeting the mTOR signaling pathway with rapamycin in cancer therapy has been less successful than expected due in part to the removal of a negative feedback loop resulting in the over-activation of the PI3K/Akt signaling pathway. As the c-Jun N-terminal kinase (JNK) signaling pathway has been found to be a functional target of PI3K, we investigate the role of JNK in the anticancer efficacy of rapamycin.Materials and Methods. The colon cancer cell line LS174T was treated with rapamycin and JNK phosphorylation was analyzed by Western Blot. Overexpression of a constitutively negative mutant of JNK in LS174T cells or treatment of LS174T cells with the JNK inhibitor SP600125 were used to determine the role of JNK in rapamycin-mediated tumor growth inhibition.Results. Treatment of LS174T cells with rapamycin resulted in the phosphorylation of JNK as observed by Western Blot. The expression of a negative mutant of JNK in LS174T cells or treatment of LS174T cells with SP600125 enhanced the antiproliferative effects of rapamycin. In addition, in vivo, the antitumor activity of rapamycin was potentiated on LS174T tumor xenografts that expressed the dominant negative mutant of JNK.Conclusions. Taken together, these results show that rapamycin-induced JNK phosphorylation and activation reduces the antitumor efficacy of rapamycin in LS174T cells. (C) 2011 Elsevier Inc. All rights reserved.
Pubmed
Web of science
Open Access
Oui
Création de la notice
06/05/2011 15:48
Dernière modification de la notice
08/05/2019 21:21
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