Bone morphogenetic protein (BMP)-6 signaling and BMP antagonist noggin in prostate cancer.
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.
Haudenschild
Dominik R
DR
Center for Tissue Regeneration and Repair, Department of Orthopedic Surgery, School of Medicine, University of California, Davis, Sacramento, California 95817, USA.
Palmer
Sabrina M
SM
Moseley
Timothy A
TA
You
Zongbing
Z
Reddi
A Hari
AH
D001483:Base Sequence; D055418:Bone Morphogenetic Protein 6; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002352:Carrier Proteins; D002455:Cell Division; D045744:Cell Line, Tumor; D017931:DNA Primers; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D011506:Proteins / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D000099176:Noggin Protein
D055418:Bone Morphogenetic Protein 6; D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D017931:DNA Primers; D011506:Proteins; D000099176:Noggin Protein; C525816:BMP6 protein, human