Downregulated GBX2 gene suppresses proliferation, invasion and angiogenesis of breast cancer cells through inhibiting the Wnt/β-catenin signaling pathway.

OBJECTIVE: Gastrulation brain homeobox 2 (GBX2), a gene involved in mid/hindbrain region, has been revealed as one of the oncogene associated with certain cancers, as an example being prostate cancer. However, despite years of worldwide research, the underlying mechanism of GBX2 as well as its significance in breast cancer still remains unclear. Therefore, the present study evaluates the abilities of GBX gene silencing providing for the proliferation, invasion and angiogenesis of breast cancer cells by way of the Wnt/β-catenin signaling pathway.

METHODS: We employed a microarray analysis to screen out differentially expressed genes relative to breast cancer. Moreover, we retrieved GBX2 expression in breast cancer to find out the relationship between GBX2 expression and prognosis in breast cancer. We performed RT-qPCR to screen out cell lines with high GBX2 expression. Subsequently, both RT-qPCR and western blot analysis were employed so as to measure the combination of the mRNA and protein expressions of GBX2, β-catenin, vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-2, and MMP-9. The effect that GBX2 gene silencing and the Wnt/β-catenin signaling pathway had on cell proliferation, invasion, angiogenesis, and tumorigenic ability were evaluated.

RESULTS: GBX2 gene was also identified having played a role in breast cancer development due to its association with the Wnt/β-catenin signaling pathway. GBX2 gene silencing was found to be an inhibitor for the mRNA and protein expressions regulating β-catenin, VEGF, MMP-2, and MMP-9. Cell proliferation, invasion, angiogenesis, as well as tumorigenic ability in breast cancer were investigated and found to have been suppressed by the GBX2 gene silencing or inactivation of the Wnt/β-catenin signaling pathway.

CONCLUSION: The study has made an attempt to provide evidence to the idea that GBX2 gene silencing has an inhibition effect on the proliferation, invasion and angiogenesis of the breast cancer cells by inhibiting the activation of the Wnt/β-catenin signaling pathway.