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JAK kinases overexpression promotes in vitro cell transformation

Oncogene volume 27, pages 1511–1519 (2008)Cite this article

Abstract

Constitutive activation of the JAK-STAT pathway is frequent in cancer and contributes to oncogenesis. Here, we took advantage of the Ba/F3 cell line, a murine proB cell line dependent on IL-3 for growth, to analyse mechanisms of constitutive STAT activation in vitro. Cytokine-independent and tumorigenic Ba/F3 cell lines were derived from a two-step selection process. Cells transfected with a defective IL-9 receptor acquire IL-9 responsiveness during a first step of selection, and progress after a second selection step to autonomously growing tumorigenic cells. Microarray analysis pointed to JAK1 overexpression as a key genetic event in this transformation. Overexpression of JAK1 not only increased the sensitivity to IL-9 but also allowed a second selection step toward cytokine-independent growth with constitutive STAT activation. This progression was dependent on a functional FERM and kinase JAK1 domain. Similar results were observed after JAK2, JAK3 and TYK2 overexpression. All autonomous cell lines showed an activation of STAT5, ERK1–2 and AKT but only TYK2-overexpressing cell lines showed a constitutive activation of STAT3. Thus, JAK overexpression can be considered as one of the oncogenic events leading to the constitutive activation of the JAK-STAT pathway.

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Acknowledgements

This work was supported in part by the Belgian Federal Service for Scientific, Technical, and Cultural Affairs, by the Actions de Recherche Concertées of the Communauté Francaise de Belgique and the operation Télévie. LK is a postdoctoral researcher and SC a research associate with the Fonds National de la Recherche Scientifique, Belgium.

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Authors and Affiliations

  1. Ludwig Institute for Cancer Research, Brussels Branch, Brussels, Belgium

    L Knoops, T Hornakova, Y Royer, S N Constantinescu & J-C Renauld

  2. de Duve Institute, Université catholique de Louvain, Brussels, Belgium

    L Knoops, T Hornakova, Y Royer, S N Constantinescu & J-C Renauld

  3. Division of Hematology, Cliniques Universitaires Saint-Luc, Brussels, Belgium

    L Knoops

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  1. L Knoops
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  2. T Hornakova
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Correspondence to J-C Renauld.

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Knoops, L., Hornakova, T., Royer, Y. et al. JAK kinases overexpression promotes in vitro cell transformation. Oncogene 27, 1511–1519 (2008). https://doi.org/10.1038/sj.onc.1210800

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