Overexpression of a dominant negative type II bone morphogenetic protein receptor inhibits the growth of human breast cancer cells.
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.
Pouliot
Frédéric
F
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.
Blais
Alexandre
A
Labrie
Claude
C
D055396:Bone Morphogenetic Protein 2; D052006:Bone Morphogenetic Protein Receptors, Type II; D019485:Bone Morphogenetic Proteins / Q000378:metabolism / Q000502:physiology; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D002453:Cell Cycle / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology; D006131:Growth Inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D006801:Humans; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051785:Smad Proteins; D051898:Smad1 Protein; D015534:Trans-Activators / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology; D014162:Transfection; D016212:Transforming Growth Factor beta; D014407:Tumor Cells, Cultured
C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; D006131:Growth Inhibitors; C497399:SMAD1 protein, human; D051785:Smad Proteins; D051898:Smad1 Protein; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; C498218:BMPR2 protein, human; D052006:Bone Morphogenetic Protein Receptors, Type II