Alternative titles; symbols
HGNC Approved Gene Symbol: HOXB9
Cytogenetic location: 17q21.32 Genomic coordinates (GRCh38): 17:48,621,156-48,626,358 (from NCBI)
About 200 homeobox genes in humans code for transcription factors, and those that are grouped into clusters, like HOXB9, are generally involved in the regulation of embryonal development (Nagel et al., 2007). See 142960.
Nagel et al. (2007) stated that Hoxb9 expression is upregulated during neural tube development in embryonal Xenopus. Using expression profiling and RT-PCR, they found that HOXB9 expression was also upregulated in a significant number of hematopoietic cell lines, predominantly those originating from Hodgkin lymphoma (236000), anaplastic large cell lymphoma, and mediastinal large B-cell lymphoma. Analysis of HOXB9 regulation in Hodgkin lymphoma cell lines revealed regulation of HOXB9 by E2F3A (E2F3; 600427), ERK5 (MAPK7 602521), PI3 kinase (see 601232), and JAK (see 147795)/STAT (see 600555) signaling.
Using in situ hybridization, Hayashida et al. (2010) found that HOXB9 expression in normal breast epithelium was restricted to the basal and luminal cells, with no stromal expression. In a significant fraction of breast cancers, specifically those of high histologic grade, HOXB9 expression was elevated. Expression of HOXB9 in both breast cancer and nontransformed mammary epithelial cells led to the expression of TGF-beta (see 190180), ERBB ligands (see EGFR, 131550), and several angiogenic factors, resulting in induction of mesenchymal cell fate, invasion, and angiogenesis. In mouse tumor xenograft models, HOXB9 expression promoted increased neovascularization and tumor metastasis to the lung.
Chiba et al. (2012) found that expression of HOXB9 in MCF10A breast cancer cells and in human mammary epithelial cells induced spontaneous DNA damage, with increased formation of phosphorylated H2AX (601772)- and 53BP1 (605230)-positive nuclear foci and enhanced DNA double-strand break repair. Expression of HOXB9 also conferred resistance to ionizing irradiation in transfected cells by promoting ATM (607585) activation and DNA double-strand break repair via a TGF-beta-dependent mechanism.
Using FISH, Nagel et al. (2007) mapped the HOXB9 gene to the HOXB gene cluster on chromosome 17q21.
Chiba, N., Comaills, V., Shiotani, B., Takahashi, F., Shimada, T., Tajima, K., Winokur, D., Hayashida, T., Willers, H., Brachtel, E., Vivanco, M. M., Haber, D. A., Zou, L., Maheswaran, S. Homeobox B9 induces epithelial-to-mesenchymal transition-associated radioresistance by accelerating DNA damage responses. Proc. Nat. Acad. Sci. 109: 2760-2765, 2012. [PubMed: 21930940] [Full Text: https://doi.org/10.1073/pnas.1018867108]
Hayashida, T., Takahashi, F., Chiba, N., Brachtel, E., Takahashi, M., Godin-Heymann, N., Gross, K. W., Vivanco, M. M., Wijendran, V., Shioda, T., Sgroi, D., Donahoe, P. K., Maheswaran, S. HOXB9, a gene overexpressed in breast cancer, promotes tumorigenicity and lung metastasis. Proc. Nat. Acad. Sci. 107: 1100-1105, 2010. [PubMed: 20080567] [Full Text: https://doi.org/10.1073/pnas.0912710107]
Nagel, S., Burek, C., Venturini, L., Scherr, M., Quentmeier, H., Meyer, C., Rosenwald, A., Drexler, H. G., MacLeod, R. A. F. Comprehensive analysis of homeobox genes in Hodgkin lymphoma cell lines identifies dysregulated expression of HOXB9 mediated via ERK5 signaling and BMI1. Blood 109: 3015-3023, 2007. [PubMed: 17148583] [Full Text: https://doi.org/10.1182/blood-2006-08-044347]