Steger J, Füller E, Garcia-Cuellar MP, Hetzner K, Slany R (2015)
Publication Status: Published
Publication Type: Journal article, Original article
Publication year: 2015
Publisher: Nature Publishing Group
Book Volume: 29
Pages Range: 901-908
Journal Issue: 4
DOI: 10.1038/leu.2014.287
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.
APA:
Steger, J., Füller, E., Garcia-Cuellar, M.-P., Hetzner, K., & Slany, R. (2015). Insulin-like growth factor 1 is a direct HOXA9 target important for hematopoietic transformation. Leukemia, 29(4), 901-908. https://doi.org/10.1038/leu.2014.287
MLA:
Steger, Julia, et al. "Insulin-like growth factor 1 is a direct HOXA9 target important for hematopoietic transformation." Leukemia 29.4 (2015): 901-908.
BibTeX: Download