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Differential effects of X-ALK fusion proteins on proliferation, transformation, and invasion properties of NIH3T3 cells

Oncogene volume 23, pages 6071–6082 (2004)Cite this article

Abstract

Majority of anaplastic large-cell lymphomas (ALCLs) are associated with the t(2;5)(p23;q35) translocation, fusing the NPM (nucleophosmin) and ALK (anaplastic lymphoma kinase) genes (NPM-ALK). Recent studies demonstrated that ALK may also be involved in variant translocations, namely, t(1;2)(q25;p23), t(2;3)(p23;q21), t(2;17)(p23;q23) and inv(2)(p23q35), which create the TPM3-ALK, TFG-ALK5, CLTC-ALK, and ATIC-ALK fusion genes, respectively. Although overexpression of NPM-ALK has previously been shown to transform fibroblasts, the transforming potential of variant X-ALK proteins has not been precisely investigated. We stably transfected the cDNAs coding for NPM-ALK, TPM3-ALK, TFG-ALK, CLTC-ALK or ATIC-ALK into nonmalignant NIH3T3 cells. All X-ALK variants are tyrosine phosphorylated and their subcellular distribution was in agreement with that observed in tumors. Moreover, our results show that the in vitro transforming capacity of NIH3T3-transfected cells are in relation to the level of X-ALK fusion proteins excepted for TPM3-ALK for which there is an inverse correlation. The differences between the five X-ALK variants with regard to proliferation rate, colony formation in soft agar, invasion, migration through the endothelial barrier and tumorigenicity seem to be due to differential activation of various signaling pathways such as PI3-kinase/AKT. These findings may have clinical implications in the pathogenesis and prognosis of ALK-positive ALCLs.

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Acknowledgements

This work was supported by the ‘Ligue Nationale Contre le Cancer’ and the ‘Comités de l'Aveyron, du Lot, de la Haute Garonne, de l'Yonne et du Gers’

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Authors and Affiliations

  1. Centre de Physiopathologie de Toulouse-Purpan. Department of ‘Oncogenesis and Signaling in Hematopoietic cells’, Inserm U.563,

    Florence Armstrong, Marie-Michèle Duplantier, Pascal Trempat, Laurence Lamant, Estelle Espinos, Claire Racaud-Sultan, Michèle Allouche & Georges Delsol

  2. U589 INSERM, Facteurs de croissance, hormones et physiopathologie cardiovasculaire, CHU Rangueil, Toulouse, France

    Corinne Hieblot & Christian Touriol

  3. Laboratory of Pathology Hospital Clinic, University of Barcelona, Villarroel 170, Barcelona, 08036, Spain

    Elias Campo

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  1. Florence Armstrong
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Correspondence to Georges Delsol.

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Armstrong, F., Duplantier, MM., Trempat, P. et al. Differential effects of X-ALK fusion proteins on proliferation, transformation, and invasion properties of NIH3T3 cells. Oncogene 23, 6071–6082 (2004). https://doi.org/10.1038/sj.onc.1207813

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