Abstract
Background
Breast cancer is a serious public health issue worldwide and, despite the advances in the understanding of this disease, its great complexity and heterogeneity still represent a major hurdle for accurate diagnosis and therapy decision-making. In addition to the biomarkers found to be useful in the prognosis a treatment of breast cancer, HOX genes have been proposed to be involved in the progression of this disease. For example, HOXB7 alterations in the expression and methylation patterns have been reported to promote breast cancer progression, most likely in a molecular subtype dependent way.
Methods
Here we induced HOXB7 overexpression in MDA-MB-231 cells, cellular model of Triple-Negative Breast Cancer, and evaluated the phenotypic changes in cell viability, morphogenesis, migration, invasion and formation of colonies. We also evaluated the expression of putative downstream targets and their direct binding to HOXB7 by Chip-qPCR in HOXB7-overexpressing cells and controls, namely CTNNB1, EGFR, FGF2, CDH1, DNMT3B and COMMD7.
Result
During the phenotypic characterization of the HOXB7-overexpressing cells, we found consistently a less aggressive behavior represented by lower cell viability, inhibition of cell migration, invasion and attachment-independent colony formation capacities added to the more compact and organized spheroids growth in 3D culture. In addition, we detected that these phenotypic changes may relate to the direct or indirect interaction of the HOXB7 protein with CTNNB1, EGFR, FGF2, CDH1, DNMT3B and COMMD7 genes.
Conclusion
Taken together, these results highlight the plasticity of the HOXB7 function in breast cancer, according to the cellular genetic background and expression levels and provide evidence that in triple-negative breast cancer cells, HOXB7 overexpression has the potential to promote less aggressive phenotypes.
17β-estradiol-induced growth of triple-negative breast cancer cells is prevented by the reduction of GPER expression after treatment with gefitinib
