Bone morphogenetic protein 2 stimulation of tumor growth involves the activation of Smad-1/5.

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.

• Authors: E M Langenfeld, Y Kong, J Langenfeld
• Journal: Oncogene (Oncogene) Vol. 25 Issue 5 Pg. 685-92 (Feb 02 2006) ISSN: 0950-9232 [Print] England
• PMID: 16247476 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• BMP2 protein, human
• Bmp2 protein, mouse
• Bone Morphogenetic Protein 2
• Bone Morphogenetic Proteins
• DNA Primers
• ID1 protein, human
• Inhibitor of Differentiation Protein 1
• Smad1 Protein
• Smad5 Protein
• Transforming Growth Factor beta

Topics

• Animals
• Base Sequence
• Blotting, Western
• Bone Morphogenetic Protein 2
• Bone Morphogenetic Proteins (physiology)
• Cell Line
• Cell Proliferation
• DNA Primers
• Humans
• Immunohistochemistry
• Inhibitor of Differentiation Protein 1 (metabolism)
• Mice
• Polymerase Chain Reaction
• Smad1 Protein (metabolism)
• Smad5 Protein (metabolism)
• Transforming Growth Factor beta (physiology)