BMP7 influences proliferation, migration, and invasion of breast cancer cells

Bone morphogenetic protein 7 (BMP7) is a signaling molecule originally identified based on its ability to form bone. It is essential during development, and more recently has also been implicated in cancer pathogenesis. We have recently shown that BMP7 is overexpressed in breast cancer, and that this increased expression is associated with early bone metastasis formation. In the present study, we explored the possible contribution of BMP7 function to the breast cancer cell phenotype. A two-way approach was applied in which BMP7 was silenced using RNA interference in three cell lines with high endogenous expression or, conversely, exogenous BMP7 was added to the growth medium of five cell lines with low or no BMP7 expression. These manipulations led to diverse cell line-specific phenotypic responses. BMP7 manipulation increased cell growth in two cell lines (BT-474, MDA-MB-231), and BMP7 treatment led to reduced growth in four cell lines (HCC1954, MDA-MB-361, T-47D, and ZR-75-30). Growth changes were due to distinct mechanisms since BMP7 silencing led to growth inhibition via G1 arrest in BT-474 cells, whereas BMP7 treatment protected MDA-MB-231 cells from apoptosis. Furthermore, BMP7 stimulation altered the MDA-MB-231 phenotype by inducing a distinct 2.3-fold increase in cell migration and an even more dramatic 3.9-fold increase in cell invasion. In conclusion, BMP7 can promote and inhibit cell growth in breast cancer cell lines and, in a suitable environment, can also considerably induce breast cancer cell migration and invasion. (C) 2008 Elsevier Ireland Ltd. All rights reserved.