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STAT3 activation is required for Asp816 mutant c-Kit induced tumorigenicity

Oncogene volume 20, pages 4528–4536 (2001)Cite this article

Abstract

Activating mutations of c-kit at codon 816 (Asp816) have been identified in variety of malignancies, including acute myeloid leukemia (AML), mastocytosis and germ cell tumors. The mutant c-Kit receptor confers cytokine independence and induces tumorigenicity. However, the molecular mechanisms, particularly the changes in the signal transduction pathways, responsible for these biological effects induced by mutant c-Kit are largely undefined. Using the human embryonic kidney cell line, 293, we show in the current report that constitutive activation of STAT3 and STAT1 is associated with D816H mutant c-Kit. Transfection of dominant negative STAT3, but not STAT1 inhibits mutant c-Kit mediated anchorage-independent growth in vitro and tumor formation in vivo. Expression of constitutively activated STAT3 restores the mutant c-Kit receptor's transforming ability in 293 cells. These results demonstrate that activation of STAT3 by Asp816 mutant c-Kit is required for the anchorage-independent growth and tumorigenicity induced by Asp816 mutant c-Kit.

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Acknowledgements

This work was supported by the Fellowship Award from Leukemia Research Foundation to Z-Q Ning and institutional grants to RJ Arceci.

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Authors and Affiliations

  1. Division of Hematology/Oncology, Children's Hospital Medical Center, Cincinnati, 45229, Ohio OH, USA

    Zhi-Qiang Ning, Jin Li & Myc McGuinness

  2. Division of Pediatric Oncology, Johns Hopkins Oncology Center, Baltimore, 21231, Maryland MD, USA

    Robert J Arceci

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  1. Zhi-Qiang Ning
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  2. Jin Li
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Ning, ZQ., Li, J., McGuinness, M. et al. STAT3 activation is required for Asp816 mutant c-Kit induced tumorigenicity. Oncogene 20, 4528–4536 (2001). https://doi.org/10.1038/sj.onc.1204590

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