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Functional characterization of Wilms tumor-suppressor WTX and tumor-associated mutants

Oncogene volume 30, pages 832–842 (2011)Cite this article

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Abstract

The WTX, Wilms tumor-associated tumor-suppressor gene, is present on the X chromosome and a single WTX mutation may be sufficient to promote carcinogenesis. Unlike the WT1 tumor suppressor, a transcription factor, WTX lacks conserved functional protein domains. To study the function of WTX, we constructed inducible cell lines expressing WTX and tumor-associated WTX mutants. Induction of WTX inhibited cell growth and caused G1/G0 arrest. In contrast, a short, tumor-associated truncation mutant of WTX358 only slightly inhibited cell growth without a significant cell-cycle arrest, although expression of a longer truncation mutant WTX565 led to the growth inhibition and cell-cycle arrest to a similar extent as wild-type WTX. Like WT1, WTX slowed growth and caused cell-cycle arrest through p21 induction. Gene expression profiling showed that these two tumor-suppressors regulated genes in similar pathways, including those implicated in control of the cellular growth, cell cycle, cell death, cancer and cardiovascular system development. When gene expression changes mediated by wild-type WTX were compared with those affected by mutant forms, WTX565 showed a 55% overlap (228 genes) in differentially regulated genes, whereas WTX358 regulated only two genes affected by wild-type WTX, implying that amino-acid residues 358–561 are critical for WTX function.

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Acknowledgements

This work is supported by a grant from the Northwestern Memorial Foundation.

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  1. Division of Hematology/Oncology, Department of Medicine, Feinberg School of Medicine, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA

    M K-H Kim, D J Min, M Rabin & J D Licht

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  1. M K-H Kim
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  2. D J Min
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Correspondence to J D Licht.

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Kim, MH., Min, D., Rabin, M. et al. Functional characterization of Wilms tumor-suppressor WTX and tumor-associated mutants. Oncogene 30, 832–842 (2011). https://doi.org/10.1038/onc.2010.452

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