Bone morphogenetic protein 2 stimulation of tumor growth involves the activation of Smad-1/5
- 10 October 2005
- journal article
- Published by Springer Science and Business Media LLC in Oncogene
- Vol. 25 (5), 685-692
- https://doi.org/10.1038/sj.onc.1209110
Abstract
Morphogenetic protein 2 (BMP-2) is normally expressed in the embryo promoting the development of several organs. Aberrant expression of BMP-2 occurs in approximately 98% of lung carcinomas, however, its role in regulating tumor growth is poorly understood. We show that BMP-2 induces Id-1 expression in lung cancer cell lines through its activation of Smad-1/5, which is dependent on cell culture conditions. A549 cells in DMEM/5% FCS BMP-2 activated Smad-1/5 and caused a transient increase in proliferation. In serum-free medium, BMP-2 induced significantly less Smad-1/5 activation and Id-1 expression, and produced significant growth inhibition. The affect of BMP-2 on tumor growth in vivo was substantially more significant. Recombinant BMP-2 coinjected with A549 cells, into nude mice increased proliferation and produced an increase in Id-1 expression. Forced expression of BMP-2 in A549 cells significantly enhanced tumor growth in the lungs following intravenous injection but not of subcutaneous tumors. Tumors in the lung were found to have an activated Smad-1/5 and expressed Id-1. Subcutaneous tumors expressed less activated Smad-1/5 and Id-1 than that of controls. Human lung carcinomas were also found to express an activated Smad-1/5 and Id-1. We provide evidence that BMP-2 promotes tumor growth. This paper highlights that cell culture experiments may not reveal the full biological affects of BMP-2, and its activity varies depending of the local environment.Keywords
This publication has 39 references indexed in Scilit:
- Over-expression of Id-1 induces cell proliferation in hepatocellular carcinoma through inactivation of p16INK4a/RB pathwayCarcinogenesis: Integrative Cancer Research, 2003
- An essential role of Bmp4 in the atrioventricular septation of the mouse heartGenes & Development, 2003
- Gene-expression profiles predict survival of patients with lung adenocarcinomaNature Medicine, 2002
- Phosphorylation of three regulatory serines of Tob by Erk1 and Erk2 is required for Ras-mediated cell proliferation and transformationGenes & Development, 2002
- Stimulation of Smad1 Transcriptional Activity by Ras-Extracellular Signal-Regulated Kinase Pathway: A Possible Mechanism for Collagen-Dependent Osteoblastic DifferentiationJournal of Bone and Mineral Research, 2002
- Bone Morphogenetic Protein-2 Blocks MDA MB 231 Human Breast Cancer Cell Proliferation by Inhibiting Cyclin-Dependent Kinase-Mediated Retinoblastoma Protein PhosphorylationBiochemical and Biophysical Research Communications, 2000
- Involvement of ERK in BMP-2 Induced Osteoblastic Differentiation of Mesenchymal Progenitor Cell Line C3H10T1/2Biochemical and Biophysical Research Communications, 2000
- Coordinated Expression of Noggin and Bone Morphogenetic Proteins (BMPs) During Early Skeletogenesis and Induction of Noggin Expression by BMP-7Journal of Bone and Mineral Research, 1999
- Intracellular signaling of osteogenic protein-1 through Smad5 activationJournal of Cellular Physiology, 1998
- Direct and Long-Range Action of a DPP Morphogen GradientCell, 1996