BMP-6 inhibits the metastasis of MDA-MB-231 breast cancer cells by regulating MMP-1 expression

Hu,Fen; Zhang,Yunfeng; Li,Mi; Zhao,Lina; Chen,Jing; Yang,Shuang; Zhang,Xiujun

doi:10.3892/or.2015.4540

BMP-6 inhibits the metastasis of MDA-MB-231 breast cancer cells by regulating MMP-1 expression

Authors:
- Fen Hu
- Yunfeng Zhang
- Mi Li
- Lina Zhao
- Jing Chen
- Shuang Yang
- Xiujun Zhang
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Affiliations: College of Life Sciences, North China University of Science and Technology, Tangshan, Hebei 063000, P.R. China, Department of Life Sciences, Tangshan Normal University, Tangshan, Hebei 063000, P.R. China, Medical College of Nankai University, Tianjin 300071, P.R. China, College of Psychology, North China University of Science and Technology, Tangshan, Hebei 063000, P.R. China
Published online on: December 31, 2015 https://doi.org/10.3892/or.2015.4540
Pages: 1823-1830

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Abstract

Bone morphogenetic protein-6 (BMP-6) is a multifunctional molecule with distinct abilities in embryogenesis and organogenesis. In the present study, our results showed that the rate of BMP-6-negative expression was 30.56% in breast cancer tissues, but was 9.58% in normal tissues by immunohistochemical staining. This implied that BMP-6 expression is absent in breast cancer tissues and may suppress breast cancer metastasis. In addition, stable overexpression of BMP-6 in MDA-MB‑231 cells was established to analyze the metastatic ability. The Boyden chamber assay showed that BMP-6 inhibited the migration and invasion of MDA-MB-231 cells. Moreover, real-time PCR analysis showed that BMP-6 markedly downregulated matrix metalloproteinase-1 (MMP-1) expression at both the mRNA and protein levels in the MDA-MB‑231 cells. Importantly, the results of luciferase and CHIP assays revealed that BMP-6 inhibited MMP-1 promoter activity through the AP-1 response element. In MDA-MB-231 cells treated with BMP-6, a significant decrease in the recruitment of AP-1 components, c-Jun/c-Fos, to the endogenous MMP-1 promoter was noted. We also demonstrated that BMP-6 inhibited the invasion of MDA-MB-231 cells, and this effect was significantly attenuated by overexpression of MMP-1. In contrast, MMP-1 knockdown by RNA interference or MMP-1 inhibitor exhibited an opposite effect. These observations suggest a novel role of BMP-6 in the inhibition of breast cancer metastasis by regulating secretion of MMPs in the tumor microenvironment.

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