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Oncogenes, Fusion Genes and Tumor Suppressor Genes

Insulin-like growth factor 1 is a direct HOXA9 target important for hematopoietic transformation

Leukemia volume 29, pages 901–908 (2015)Cite this article

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Abstract

HOX homeobox proteins are key oncogenic drivers in hematopoietic malignancies. Here we demonstrate that HOXA1, HOXA6 and predominantly HOXA9 are able to induce the production of insulin-like growth factor 1 (Igf1). In chromatin immunoprecipitations, HOXA9 bound directly to the putative promoter and a DNase-hypersensitive region in the first intron of the Igf1 gene. Transcription rates of the Igf1 gene paralleled HOXA9 activity. Primary cells transformed by HOXA9 expressed functional Igf1 receptors and activated the protein kinase Akt in response to Igf1 stimulation, suggesting the existence of an autocrine signaling loop. Genomic deletion of the Igf1 gene by Cre-mediated recombination increased sensitivity toward apoptosis after serum starvation. In addition, the leukemogenic potential of Igf1-negative, HOXA9-transformed cells was impaired, leading to a significant delay in disease development on transplantation into recipient animals.

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Acknowledgements

We thank Renate Zimmermann for technical assistance and Constanze Breitinger for help in early stages of this study. This work was supported by research funding from the Deutsche Forschungsgemeinschaft (SL27/8-1) to RKS.

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Authors and Affiliations

  1. Department of Genetics, University of Erlangen, Erlangen, Germany

    J Steger, E Füller, M-P Garcia-Cuellar, K Hetzner & R K Slany

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  1. J Steger
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  2. E Füller
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  3. M-P Garcia-Cuellar
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Correspondence to R K Slany.

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Steger, J., Füller, E., Garcia-Cuellar, MP. et al. Insulin-like growth factor 1 is a direct HOXA9 target important for hematopoietic transformation. Leukemia 29, 901–908 (2015). https://doi.org/10.1038/leu.2014.287

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