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Overexpression of a Dominant Negative Type II Bone Morphogenetic Protein Receptor Inhibits the Growth of Human Breast Cancer Cells¹

Oncology and Molecular Endocrinology Research Center, Centre Hospitalier de l’Université Loval Research Center Centre Hospitalier Universitaire de Quebec and Laval University, Sainte-Foy, Quebec, G1V 4G2 Canada

Bone morphogenetic proteins (BMPs) exert cell type-specific effects on cell proliferation. To clarify the role of the BMP pathway in human breast cancer cells, we used a dominant negative strategy with a truncated human type II BMP receptor (DN-BMPRII; amino acid 1–172) fused to the NH₂ terminus of enhanced green fluorescent protein. Transient overexpression of DN-BMPRII interfered with BMP-2-induced Smad1 transcriptional activity and caused cells to accumulate in G₁. Stable cell lines that constitutively overexpressed DN-BMPRII were resistant to BMP-2-induced Smad1 phosphorylation and proliferated much more slowly than control stable cell lines. These results suggest that BMPs interacting with type II BMP receptors contribute to the proliferation and/or survival of human breast cancer cells.

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