Overexpression of a dominant negative type II bone morphogenetic protein receptor inhibits the growth of human breast cancer cells

Frédéric Pouliot; Alexandre Blais; Claude Labrie

Overexpression of a dominant negative type II bone morphogenetic protein receptor inhibits the growth of human breast cancer cells

Cancer Res. 2003 Jan 15;63(2):277-81.

Authors

Frédéric Pouliot¹, Alexandre Blais, Claude Labrie

Affiliation

¹ 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.

PMID: 12543773

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Bone Morphogenetic Protein 2
Bone Morphogenetic Protein Receptors, Type II
Bone Morphogenetic Proteins / metabolism
Bone Morphogenetic Proteins / physiology
Breast Neoplasms / genetics
Breast Neoplasms / metabolism*
Breast Neoplasms / pathology*
Cell Cycle / physiology
Cell Division / physiology
DNA-Binding Proteins / antagonists & inhibitors
DNA-Binding Proteins / metabolism
DNA-Binding Proteins / physiology
Growth Inhibitors / biosynthesis
Growth Inhibitors / genetics
Growth Inhibitors / physiology
Humans
Phosphorylation
Protein Serine-Threonine Kinases / biosynthesis
Protein Serine-Threonine Kinases / genetics
Protein Serine-Threonine Kinases / physiology*
Smad Proteins
Smad1 Protein
Trans-Activators / antagonists & inhibitors
Trans-Activators / metabolism
Trans-Activators / physiology
Transfection
Transforming Growth Factor beta*
Tumor Cells, Cultured

Substances

BMP2 protein, human
Bone Morphogenetic Protein 2
Bone Morphogenetic Proteins
DNA-Binding Proteins
Growth Inhibitors
SMAD1 protein, human
Smad Proteins
Smad1 Protein
Trans-Activators
Transforming Growth Factor beta
Protein Serine-Threonine Kinases
BMPR2 protein, human
Bone Morphogenetic Protein Receptors, Type II