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Acute Leukemias

GATA-1 and GATA-2 binding to 3′ enhancer of WT1 gene is essential for its transcription in acute leukemia and solid tumor cell lines

Leukemia volume 23, pages 1270–1277 (2009)Cite this article

Abstract

Although oncogenic functions and the clinical significance of Wilms tumor 1 (WT1) have been extensively studied in acute leukemia, the regulatory mechanism of its transcription still remains to be determined. We found a significant correlation among the amounts of WT1, GATA-1 and GATA-2 mRNAs from leukemia and solid tumor cell lines. Overexpression and small interfering RNA (siRNA) transfection experiments of GATA-1 and GATA-2 showed that these GATA transcription factors could induce WT1 expression. Promoter analysis showed that the 5′ promoter did not explain the different WT1 mRNA levels between cell lines. The 3′ enhancer, especially the distal sites out of six putative GATA binding sites located within the region, but not the intron 3 enhancer, were essential for the WT1 mRNA level. Electrophoretic mobility shift assay (EMSA) showed both GATA-1 and GATA-2 bound to these GATA sites. Besides acute leukemia cell lines, solid tumor cell lines including, TYK-nu-cPr also showed a high level of WT1 mRNA. We showed that GATA-2 expression is a determinant of WT1 mRNA expression in both TYK-nu-cPr cells and HL60 cells without GATA-1 expression. Taken together, these results suggest that GATA-1 and/or GATA-2 binding to a GATA site of the 3′ enhancer of WT1 played an important role in WT1 gene expression.

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Acknowledgements

We express our sincere thanks to Dr H Nagai and Ms K Hagiwara (National Hospital Organization, Nagoya Medical Center, Nagoya, Japan) and to Dr Y Oji and Dr H Sugiyama (Osaka University Graduate School of Medicine, Osaka, Japan) for providing us with cell lines and useful comments. We acknowledge Ms Y Nomura for her excellent cell-sorting work. This work was supported in part by a Grant-in-Aid for Basic Research C 16590453 and by Health and Labour Research Grants from the Ministry of Health, Labour and Welfare, Japan.

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Authors and Affiliations

  1. Department of Medical Technology, Nagoya University Graduate School of Health Sciences, Nagoya, Japan

    A Furuhata, M Murakami, H Ito, S Gao, K Yoshida, A Takagi, T Kojima & T Murate

  2. Department of Pathology, College of Life and Health Sciences, Chubu University, Kasugai, Japan

    S Sobue

  3. Department of Laboratory Medicine, Nagoya University School of Medicine, Nagoya, Japan

    R Kikuchi & T Iwasaki

  4. Division of Molecular Carcinogenesis, Nagoya University Graduate School of Medicine, Nagoya, Japan

    M Suzuki

  5. Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan

    A Abe & T Naoe

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Correspondence to T Murate.

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Furuhata, A., Murakami, M., Ito, H. et al. GATA-1 and GATA-2 binding to 3′ enhancer of WT1 gene is essential for its transcription in acute leukemia and solid tumor cell lines. Leukemia 23, 1270–1277 (2009). https://doi.org/10.1038/leu.2009.13

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