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Modulation of PI3K/Akt pathway by E1a mediates sensitivity to cisplatin

Oncogene volume 21, pages 7131–7136 (2002)Cite this article

Abstract

In order to investigate the molecular mechanisms implicated in the induction of chemo sensitivity by adenovirus E1a gene expression, we decided to investigate which signal transduction pathways could be affected by the E1a gene in Human Normal Fibroblast (IMR90). No effect was observed in SAPK pathways (p38MAPK and JNK), but E1a was able to affect the Akt activation mediated by insulin. This result was confirmed by transient transfection experiments performed in Cos-7 cells and also observed in other transformed cell lines such as A431. Furthermore, E1a expression induces a decrease in the basal status of Akt activity. Finally we demonstrated that E1a is able to block the Akt activation mediated by cisplatin and correlates with a sensitive phenotype. In summary, our data demonstrate that specific inhibition of the PI3K/Akt pathway mediates some of the biological properties of E1a such as induction of chemosensitivity.

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Acknowledgements

We appreciate the comments and helpful discussions of Drs L del Peso, J Recio and M Serrano. We also wish to thank M Hadley-Adams for his assistance with the manuscript and A Sánchez López and L Grijander for technical assistance. This work was supported by grants from FIS (01/0475) CAM (081/0005/2001). J Guinea Viniegra and VM Fernández Soria were supported by the Fondo Social Europeo from Consejeria de Educación de la Comunidad de Madrid. C Parada Cobo was supported by the Fondo de Investigaciones Sanitarias (00/9039).

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  1. Santiago Ramón y Cajal and Ricardo Sánchez-Prieto: Santiago Ramón n y Cajal and Ricardo Sánchez-Prieto have contributed equally to this work

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  1. Unidad de Patología Molecular, Clínica Puerta de Hierro, C/San Martín de Porres 4, Madrid, 28035, Spain

    Juan Guinea Viniegra, Javier Hernández Losa, Victor Javier Sánchez-Arévalo, Carlos Parada Cobo, Victor Manuel Fernández Soria, Santiago Ramón y Cajal & Ricardo Sánchez-Prieto

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  1. Juan Guinea Viniegra
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Correspondence to Santiago Ramón y Cajal or Ricardo Sánchez-Prieto.

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Viniegra, J., Losa, J., Sánchez-Arévalo, V. et al. Modulation of PI3K/Akt pathway by E1a mediates sensitivity to cisplatin. Oncogene 21, 7131–7136 (2002). https://doi.org/10.1038/sj.onc.1205934

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