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Constitutively active STAT5 variants induce growth and survival of hematopoietic cells through a PI 3-kinase/Akt dependent pathway

Oncogene volume 20, pages 2080–2090 (2001)Cite this article

Abstract

Signal Transducer and Activator of Transcription (STATs) are important mediators of cytokine and growth factor-induced signal transduction. STAT5A and STAT5B have been shown to play a role in survival and proliferation of hematopoietic cells both in vitro and in vivo and to contribute to the growth and viability of cells transformed by the TEL-JAK2 oncoprotein. In this study, we investigated the molecular mechanisms by which constitutively active STAT5 proteins induce cell proliferation and survival of Ba/F3 cell lines expressing either dominant positive STAT5A or STAT5B variants or TEL-JAK2 or TEL-ABL fusion proteins. Our results showed that active STAT5 constitutively interacted with p85, the regulatory subunit of the PI 3-kinase. A constitutive activity of the PI 3-kinase/Akt pathway was observed in these cells and required for their cell cycle progression. In contrast, while activity of the PI 3-kinase/Akt pathway was required for survival of Ba/F3 cells expressing the constitutively active forms of STAT5A or STAT5B, it was dispensable for cells transformed by TEL-JAK2 or TEL–ABL fusion proteins, suggesting that additional survival pathways take place in these transformed cells.

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Acknowledgements

The authors would like to thank Drs Tosio Kitamura for providing the STAT5A1*6 and STAT5B 1*6 cDNAs, P Mayeux for the Ba/F3Epo-R cell, S Fichelson for the human erythroid progenitors and the Faculdade de Farmácia at Lisbon. This work was supported by ARC (Association de Recherche contre le Cancer) and Fondation de France. SC Rosa Santos is supported by Praxis XXI.

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Authors and Affiliations

  1. Institut Cochin de Génétique Moléculaire (ICGM), Institut National de la Santé et de la Recherche Médicale (INSERM U363), Hôpital Cochin, 27 rue du Fbg St Jacques, Paris, 75014, France

    Susana Constantino Rosa Santos, Isabelle Bouchaert, Sylvie Gisselbrecht & Fabrice Gouilleux

  2. CEPH INSERM U434, 27 rue J. Dodu, Paris, 75010, France

    Virginie Lacronique, Richard Monni & Olivier Bernard

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  1. Susana Constantino Rosa Santos
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  7. Fabrice Gouilleux
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Santos, S., Lacronique, V., Bouchaert, I. et al. Constitutively active STAT5 variants induce growth and survival of hematopoietic cells through a PI 3-kinase/Akt dependent pathway. Oncogene 20, 2080–2090 (2001). https://doi.org/10.1038/sj.onc.1204308

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