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  • Original Paper
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MAPK phosphatase DUSP16/MKP-7, a candidate tumor suppressor for chromosome region 12p12–13, reduces BCR-ABL-induced transformation

Oncogene volume 22, pages 7728–7736 (2003)Cite this article

Abstract

Recurrent chromosome 12p deletions are associated with distinct tumor types and suggest the presence of a tumor suppressor gene (TSG). Previously, we mapped an EST with similarity to a protein tyrosine phosphatase to the minimally deleted region for all these neoplasms. The corresponding gene, DUSP16/MKP-7, was recently shown to code for a mitogen-activated protein kinase phosphatase, suggestive for a function as tumor suppressor. Overexpression of DUSP16 in BCR-ABL-transformed Rat-1 fibroblasts reduces their transforming capacity in vitro and in vivo via downregulation of BCR-ABL-induced JNK activation. A role for DUSP16 as a regulator of JNK signaling was further demonstrated via overexpression in Ba/F3 cells, which increased their antiapoptosis. However, no inactivating mutations could be detected in leukemia patients hemizygous for DUSP16, and the effect of hemizygosity on DUSP16 expression level could not be assessed due to the variability of DUSP16 transcript levels observed in leukaemia cell lines and in patients. Taken together, the functional data point to a context-dependent role for DUSP16 on cell transformation and apoptosis, reflecting the dual role of JNK, and therefore suggest that DUSP16 might be haploinsufficient for tumor suppression.

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Acknowledgements

We thank Anne Hagemeijer, Iwona Wlodarska and Michel Stul for providing us patient material, and Vic Van Duppen for the FACS analysis. This work was supported by Grants G0121.00 and G0368.02 from ‘FWO-Vlaanderen’, Belgium (to PM) and GOA Research Fund KU Leuven (to JG). Inge Hoornaert is supported by the ‘IWT-Vlaanderen’, Belgium. Mathijs Baens is a ‘Postdoctoraal Onderzoeker’ of the ‘FWO-Vlaanderen’, Belgium.

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Authors and Affiliations

  1. Department of Human Genetics, Human Genome Laboratory, Flanders Interuniversity Institute for Biotechnology (VIB), Katholieke Universiteit Leuven, Herestraat 49, Leuven, B-3000, Belgium

    Inge Hoornaert, Peter Marynen & Mathijs Baens

  2. Department of Molecular Cell Biology, Division of Biochemistry, Katholieke Universiteit Leuven, Herestraat 49, Leuven, B-3000, Belgium

    Jozef Goris

  3. Department of Pathology, Katholieke Universiteit Leuven, Herestraat 49, Leuven, B-3000, Belgium

    Raf Sciot

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  1. Inge Hoornaert
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Correspondence to Mathijs Baens.

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Hoornaert, I., Marynen, P., Goris, J. et al. MAPK phosphatase DUSP16/MKP-7, a candidate tumor suppressor for chromosome region 12p12–13, reduces BCR-ABL-induced transformation. Oncogene 22, 7728–7736 (2003). https://doi.org/10.1038/sj.onc.1207089

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