Tatsuki, Y.; Mizuta, K.; Inoue, M.; Takahashi, O.; Tanaka, J.; Haraguchi, K.; Tsurushima, H.; Yoshioka, I.; Kokabu, S.; Habu, M.

Objective: Bone morphogenetic protein-3b (BMP-3b), also known as growth differentiation factor 10, has been implicated in tumor suppression; however, its role in breast cancer and its interaction with transforming growth factor-{beta}1 (TGF-{beta}1) signaling remain incompletely understood. Methods: Publicly available datasets were used to examine BMP-3b expression in breast lesions and its association with overall survival in patients with stage III or IV breast cancer. Human MCF-7 and murine 4T1 breast cancer cells were treated with recombinant BMP-3b. Cell proliferation, migration, invasion, epithelial-mesenchymal transition-related proteins, and TGF-{beta}1-induced Smad3 phosphorylation were assessed using Cell Counting Kit-8, scratch wound-healing, Transwell invasion, and Western blot assays. Results: BMP-3b expression was lower in ductal carcinoma in situ than in normal mammary tissue. Low BMP-3b expression was associated with poorer overall survival in patients with stage III or IV breast cancer. BMP-3b reduced proliferation of MCF-7 and 4T1 cells and inhibited migration and invasion of 4T1 cells. BMP-3b increased E-cadherin and decreased vimentin expression in both cell lines. It also attenuated TGF-{beta}1-induced migration, invasion, and Smad3 phosphorylation in 4T1 cells. Conclusions: BMP-3b suppresses malignant phenotypes of breast cancer cells and modulates TGF-{beta}1/Smad3 signaling. These findings identify BMP-3b as a potential endogenous regulator of breast cancer progression.