Abstract
BACKGROUND: Transforming growth factor-β (TGF-β) is known to promote tumor proliferation, migration, invasion, and metastasis. Bone morphogenetic proteins (BMPs) are members of the TGF-β superfamily. Several BMPs (BMP2 and BMP7) can enhance the invasion and bone metastasis of breast cancer cells. The function of BMP9, the latest discovered and most powerful osteogenetic factor, in breast cancer has not been fully elucidated. METHODS: BMP9 expression in twenty-three breast cancer patients and three breast cancer cell line types was detected by reverse transcriptase polymerase chain reaction. Changes in proliferation, apoptosis, invasion, and migration in the recombinant MDA-MB-231/BMP9 cells were detected using various assays. The assays were MTT, flow cytometry, colony forming, cell wounding, and transwell invasion. Proliferating cell nuclear antigen and terminal deoxynucleotidy transferase biotin-dUTP nick end labeling staining methods were conducted to detect whether BMP9 affected proliferation and apoptosis in xenogenic mouse models. RESULTS: Twenty-one of the twenty-three breast cancer patients had amplified BMP9 mRNA transcripts in adjacent non-tumor tissues, although BMP9 was observed in the breast cancer tissue of two patients, its expression was higher in the adjacent non-tumor tissues. BMP9 overexpression inhibited the proliferation, migration, and invasion, as well as induced the apoptosis of the breast cancer cell line MDA-MB-231 in vitro. BMP9 also inhibited tumor growth and induced apoptosis significantly in the xenogenic mouse models. CONCLUSIONS: Decreased BMP9 expression is associated with the elevated proliferation and migration of human breast cancer. BMP9 can inhibit the growth, invasion, and migration of breast cancer cells in vitro and in vivo. BMP9 is a putative tumor suppressor in breast cancer.