Abstract
The transcriptional factor Osterix is specifically expressed in bone tissues to regulate the differentiation and maturation of osteoblasts. Recent studies have also identified the expression of Osterix in a number of cancer tissues, such as kidney and lung cancers. However, the association of Osterix with the metastasis of breast cancers has never been reported. The present study, for the first time, provides evidence supporting the involvement of Osterix in breast cancer metastasis. Western blotting was employed to investigate the expression of Osterix in a number of human breast cancer cell lines with different metastatic features. Gain-of-function and loss-of-function experiments were performed in MCF7 cells (low level of metastasis) and MDA-MB-361 cells (high level of metastasis). The expression of several metastasis-associated genes was analyzed by western blotting and quantitative polymerase chain reaction. A firefly luciferase-based reporter gene assay was conducted in order to study whether Osterix regulated the promoter activities of the MMP2 and MMP9 genes, which play critical roles in cancer metastasis. The results showed that Osterix was highly expressed in the MDA-MB-231 and MDA-MB-361 cells, but was not detectable in the MCF7 cells. The overexpression of Osterix in the MCF7 cells promoted the expression of VEGF, MMP9 and β-catenin, while downregulating the expression of E-cadherin. In addition, suppression of Osterix expression in the MDA-MB-361 cells reversed the alteration of VEGF, MMP9, β-catenin and E-cadherin expression. A reporter gene assay suggested that Osterix activated MMP2 and MMP9 promoter activity. In conclusion, Osterix is involved in the metastasis of human breast cancer and may be a target for the efficient treatment of human breast cancers.