Publisher: Spandidos Publications
E-ISSN: 1792-1082|10|3|1870-1874
ISSN: 1792-1074
Source: Oncology Letters, Vol.10, Iss.3, 2015-01, pp. : 1870-1874
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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. Gainoffunction and lossoffunction experiments were performed in MCF7 cells (low level of metastasis) and MDAMB361 cells (high level of metastasis). The expression of several metastasisassociated genes was analyzed by western blotting and quantitative polymerase chain reaction. A firefly luciferasebased 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 MDAMB231 and MDAMB361 cells, but was not detectable in the MCF7 cells. The overexpression of Osterix in the MCF7 cells promoted the expression of VEGF, MMP9 and βcatenin, while downregulating the expression of Ecadherin. In addition, suppression of Osterix expression in the MDAMB361 cells reversed the alteration of VEGF, MMP9, βcatenin and Ecadherin 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.
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