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WT1 expression induces features of renal epithelial differentiation in mesenchymal fibroblasts

Oncogene volume 18, pages 417–427 (1999)Cite this article

Abstract

The WT1 tumor suppressor gene, implicated in hereditofamilial and sporadic Wilms' tumor, is required for normal renal development and is up-regulated during the mesenchymal-epithelial transition. NIH3T3 fibroblasts overexpressing WT1 were less proliferative, larger in size and more firmly attached to tissue culture plastic, suggesting an alteration of their state of differentiation. These cells were studied in vivo by subcutaneous injection into nude mice. The resulting tumors exhibited epithelioid histopathology and formed desmosome-like structures. Molecular analyses of these WT1 expressing fibroblasts grown in culture and in nude mice revealed significant alterations in the expression of many kidney epithelial markers. These studies indicate that WT1 expression can initiate features of a program of epithelial differentiation consistent with a prominent role for WT1 in the mesenchymal epithelial transition that occurs during renal development. Through this work we identified a number of novel target genes for the WT1 transcription factor, including uvomorulin, integrin α8 and perlecan, and suggest that WT1 may activate the IGF-II gene, also implicated in the development of Wilms' tumor.

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Article 01 December 2022

Zixuan Zhao, Xinyi Chen, … Hanry Yu

Abbreviations

WT1:

Wilms' tumor susceptibility gene

MET:

mesenchymal-epithelial transition

ECM:

extracellular matrix proteins

CAM:

cellular adhesion molecules

MDCK:

Madin-Darby canine kidney

HSPG:

heparan sulfate proteoglycan

IGF-II:

Insulin-like growth factor II

HGF/SF:

hepatocyte growth factor/scatter factor

RSV:

Rous sarcoma virus

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Acknowledgements

We thank Qais al-Awqati, Joan Gil, Paul Klotman, Ronald Gordon and Melissa Little for critical discussion of the manuscript; and Yan Fang, Ronald Gordon, Leslie Bruggemann and Honor O'Sullivan for technical support. This work was supported by the NIH RO1 CA59936 (JDL), The Council for Tobacco Research (JDL), and RO1 HL54184 (GFA). This is publication #240 from the Brookdale Center for Developmental and Molecular Biology.

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  1. Brookdale Center for Developmental and Molecular Biology and Department of Medicine, Box 1126, Mount Sinai School of Medicine, New York, 10029, NY, USA

    Seiyu Hosono, Xiangnong Luo, Deborah P Hyink, Lynn M Schnapp, Patricia D Wilson, Christopher R Burrow, Josina C Reddy, George F Atweh & Jonathan D Licht

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Hosono, S., Luo, X., Hyink, D. et al. WT1 expression induces features of renal epithelial differentiation in mesenchymal fibroblasts. Oncogene 18, 417–427 (1999). https://doi.org/10.1038/sj.onc.1202311

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