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

Dominik R Haudenschild, Sabrina M. Palmer, Timothy A. Moseley, Zongbing You, A Hari Reddi

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)8276-8284
Number of pages9
JournalCancer Research
Volume64
Issue number22
DOIs
StatePublished - Nov 15 2004

Fingerprint

Bone Morphogenetic Protein 6
Bone Morphogenetic Proteins
Prostatic Neoplasms
Prostate
Neoplasm Metastasis
Cell Culture Techniques
Protein Array Analysis
Cyclin-Dependent Kinases
Microarray Analysis
Reverse Transcription
Up-Regulation
Immunohistochemistry
Biopsy
Gene Expression
Bone and Bones
Polymerase Chain Reaction
Therapeutics
Growth
Proteins

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Bone morphogenetic protein (BMP)-6 signaling and BMP antagonist noggin in prostate cancer. / Haudenschild, Dominik R; Palmer, Sabrina M.; Moseley, Timothy A.; You, Zongbing; Reddi, A Hari.

In: Cancer Research, Vol. 64, No. 22, 15.11.2004, p. 8276-8284.

Research output: Contribution to journalArticle

Haudenschild, Dominik R ; Palmer, Sabrina M. ; Moseley, Timothy A. ; You, Zongbing ; Reddi, A Hari. / Bone morphogenetic protein (BMP)-6 signaling and BMP antagonist noggin in prostate cancer. In: Cancer Research. 2004 ; Vol. 64, No. 22. pp. 8276-8284.
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