Bone morphogenetic protein (BMP)-6 signaling and BMP antagonist noggin in prostate cancer.

Authors:
Prof. Dominik R Haudenschild, Ph.D.
Prof. Dominik R Haudenschild, Ph.D.
University of California Davis Medical Center
Professor
Arthritis Research
Sacramento, CA | United States
Timothy A Moseley
Timothy A Moseley
NuVasive
San Diego | United States
Zongbing You
Zongbing You
Department of Structural and Cellular Biology
New Orleans | United States

Cancer Res 2004 Nov;64(22):8276-84

Center for Tissue Regeneration and Repair, Department of Orthopedic Surgery, School of Medicine, University of California, Davis, Sacramento, California 95817, USA.

It has been proposed that the osteoblastic nature of prostate cancer skeletal metastases is due in part to elevated activity of bone morphogenetic proteins (BMPs). BMPs are osteoinductive morphogens, and elevated expression of BMP-6 correlates with skeletal metastases of prostate cancer. In this study, we investigated the expression levels of BMPs and their modulators in prostate, using microarray analysis of cell cultures and gene expression. Addition of exogenous BMP-6 to DU-145 prostate cancer cell cultures inhibited their growth by up-regulation of several cyclin-dependent kinase inhibitors such as p21/CIP, p18, and p19. Expression of noggin, a BMP antagonist, was significantly up-regulated by BMP-6 by microarray analysis and was confirmed by quantitative reverse transcription-polymerase chain reaction and at the protein level. Noggin protein was present in prostate biopsies and localized to the epithelial components of prostate by immunohistochemistry. Recombinant noggin inhibited the function of BMP-6, suggesting a negative feedback regulation of BMP activity and indicating a strategy for the development of a novel therapeutic target in the treatment of painful osteosclerotic bone metastases of prostate cancer.

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http://dx.doi.org/10.1158/0008-5472.CAN-04-2251DOI Listing

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November 2004
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24 Citations
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