Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2007-1-4
pubmed:abstractText
In addition to changes in cellular pathways, loss of differentiation is a notable feature of osteosarcoma. We hypothesized that blocks to normal differentiation may be a common feature of osteosarcoma, and may be one of many critical events that occur during oncogenesis in osteosarcoma. Furthermore, therapies that restore normal programs of differentiation may be attractive new treatment strategies for chemo-therapy and/or chemoprevention. We exposed an osteosarcoma cell line to two highly osteogenic bone morphogenetic proteins and noted increased tumor volume and no evidence of osteoinduction in vivo. We then used expression profile analysis to identify downstream targets of the osteogenic bone morphogenetic proteins, revealing up-regulation of the inhibitor of differentiation genes 1, 2, and 3, and the nuclear receptor, peroxisome proliferator activated receptor gamma. We then evaluated the use of nuclear receptor agonists, including peroxisome proliferator activated receptor gamma, to circumvent the apparent block to bone morphogenetic protein-induced differentiation in osteosarcoma cell lines. The peroxisome proliferator activated receptor gamma/retinoid X receptor agonists induced terminal differentiation in all four osteosarcoma cell lines and were synergistic when combined. In osteosarcoma cells, there are inherent blocks to normal bone morphogenetic protein-induced differentiation; however, they do not prevent nuclear receptor agonists from inducing terminal differentiation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0009-921X
pubmed:author
pubmed:issnType
Print
pubmed:volume
454
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
237-46
pubmed:dateRevised
2007-12-3
pubmed:meshHeading
pubmed-meshheading:17075380-Animals, pubmed-meshheading:17075380-Bone Morphogenetic Proteins, pubmed-meshheading:17075380-Bone Neoplasms, pubmed-meshheading:17075380-Cell Differentiation, pubmed-meshheading:17075380-Cell Line, pubmed-meshheading:17075380-Cell Line, Tumor, pubmed-meshheading:17075380-Cell Transformation, Neoplastic, pubmed-meshheading:17075380-Gene Expression Profiling, pubmed-meshheading:17075380-Gene Expression Regulation, Neoplastic, pubmed-meshheading:17075380-Humans, pubmed-meshheading:17075380-Male, pubmed-meshheading:17075380-Mice, pubmed-meshheading:17075380-Mice, Nude, pubmed-meshheading:17075380-Osteoblasts, pubmed-meshheading:17075380-Osteosarcoma, pubmed-meshheading:17075380-PPAR gamma, pubmed-meshheading:17075380-Receptors, Cytoplasmic and Nuclear, pubmed-meshheading:17075380-Retinoid X Receptors, pubmed-meshheading:17075380-Xenograft Model Antitumor Assays
pubmed:year
2007
pubmed:articleTitle
Osteosarcoma and osteoblastic differentiation: a new perspective on oncogenesis.
pubmed:affiliation
Department of Surgery, The University of Chicago Medical Center, Chicago, IL, USA. rhaydon@surgery.bsd.uchicago.edu
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural