Bone morphogenetic protein signaling in prostate cancer cell lines

Prostate cancer is the most commonly diagnosed malignancy in men and is often associated with bone metastases. Prostate cancer bone lesions can be lytic or schlerotic, with the latter predominating. Bone morphogenetic proteins (BMPs) are a family of growth factors, which may play a role in the forma...

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Bibliographic Details
Published in:Journal of cellular biochemistry 2004-01, Vol.91 (1), p.151-160
Main Authors: Brubaker, K.D., Corey, E., Brown, L.G., Vessella, R.L.
Format: Article
Language:English
Subjects:
Bone Morphogenetic Protein 2
Bone Morphogenetic Protein 4
Bone Morphogenetic Proteins - pharmacology
bone morphogenetic receptors (BMPRs)
Bone Neoplasms - metabolism
Bone Neoplasms - secondary
Cell Division - drug effects
Cyclin-Dependent Kinase Inhibitor p21
Cyclins - metabolism
DNA-Binding Proteins - metabolism
Flow Cytometry
G1 Phase - physiology
Glycoproteins - metabolism
Humans
Male
Osteoprotegerin
osteoprotegerin (OPG)
p21CIP1/WAF1
p27KIP1
Phosphorylation - drug effects
Prostatic Neoplasms - metabolism
Receptors, Cytoplasmic and Nuclear - metabolism
Receptors, Tumor Necrosis Factor
retinoblastoma (Rb)
Retinoblastoma Protein - metabolism
Signal Transduction - physiology
Smad Proteins
SMAD-1
Smad1 Protein
Trans-Activators - metabolism
Transforming Growth Factor beta
Tumor Cells, Cultured
Up-Regulation - drug effects
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Summary:Prostate cancer is the most commonly diagnosed malignancy in men and is often associated with bone metastases. Prostate cancer bone lesions can be lytic or schlerotic, with the latter predominating. Bone morphogenetic proteins (BMPs) are a family of growth factors, which may play a role in the formation of prostate cancer osteoblastic bone metastases. This study evaluated the effects of BMPs on prostate cancer cell lines. We observed growth inhibitory effects of BMP‐2 and ‐4 on LNCaP, while PC‐3 was unaffected. Flow cytometric analysis determined that LNCaP cell growth was arrested in G1 after bone morphogenetic protein‐2 treatment. Treatment of LNCaP and PC‐3 with BMP‐2 and ‐4 activated downstream signaling pathways involving SMAD‐1, up‐regulation of p21CIP1/WAF1 and changes in retinoblastoma (Rb) phosphorylation. Interestingly, bone morphogenetic protein‐2 treatment stimulated a 2.7‐fold increase in osteoprotegerin (OPG), a molecule, which inhibits osteoclastogenesis, production in PC‐3. © 2003 Wiley‐Liss, Inc.
ISSN:0730-2312
1097-4644
DOI:10.1002/jcb.10679