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IL-2 signals through Sgk1 and inhibits proliferation and apoptosis in kidney cancer cells

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Abstract

The interleukin-2 is a cytokine that is essential for lymphocytic survival and function. Ectopic expression of the IL-2 receptor in epithelial tissues has been reported previously, although the functional significance of this expression is still being investigated. We provided novel structural and functional information on the expression of the IL-2 receptor in kidney cancer cells and in other normal and neoplastic human epithelial tissues. In A-498 kidney cancer cells, we showed that IL-2 binding to its own receptor triggers a signal transduction pathway leading to the inhibition of proliferation and apoptosis. We found that the inhibition of proliferation is associated with Erk1/2 dephosphorylation, whereas the survival signals appear to be mediated by Sgk1 activation. This investigation focuses on the IL-2 induced regulation of Sgk1 and describes a role of the IL-2 receptor and Sgk1 in the regulation of epithelial tumor cell death and survival.

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Abbreviations

IL-2:

Interleukin-2

IL-2R:

Interleukin-2 Receptor

Sgk1:

Serum and glucocorticoid regulated kinase

Erk1/2:

Extracellular regulated kinase 1/2

Shc-1:

Src homology 2 domain containing

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Acknowledgments

We thank Charity Nofziger and Professor Bonnie Blazer-Yost for critical reading and helpful discussion of the manuscript, and Nicola Amodio for the caspase 8 confocal experiment’s acquisition.

This work was supported by Fondazione Carical, Cluster 04 work package 6A, Cofin 2003/20032003063143_003, Cofin 2005 /068017_004, Interlink II04C0G4EM.

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Authors and Affiliations

  1. Department of Experimental and Clinical Medicine “G. Salvatore”, University “Magna Graecia”, Campus Biomedico, Località Germaneto, Viale Europa, Catanzaro, 88100, Italy

    Rosario Amato, Miranda Menniti, Valter Agosti, Rosalia Boito, Heather M. Bond, Vito Barbieri, Pierosandro Tagliaferri, Salvatore Venuta & Nicola Perrotti

  2. Department of Pharmacobiology, University “Magna Graecia”, Catanzaro, Italy

    Nicola Costa

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  1. Rosario Amato
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  2. Miranda Menniti
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  3. Valter Agosti
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  4. Rosalia Boito
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  5. Nicola Costa
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  6. Heather M. Bond
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  9. Salvatore Venuta
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  10. Nicola Perrotti
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Correspondence to Nicola Perrotti.

Additional information

In loving memory of Salvatore Venuta, 1944–2007.

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Amato, R., Menniti, M., Agosti, V. et al. IL-2 signals through Sgk1 and inhibits proliferation and apoptosis in kidney cancer cells. J Mol Med 85, 707–721 (2007). https://doi.org/10.1007/s00109-007-0205-2

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  • DOI: https://doi.org/10.1007/s00109-007-0205-2

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