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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
2005-9-5
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pubmed:abstractText |
Alveolar rhabdomyosarcoma (ARMS) cells express high levels of PAX3-FKHR and IGF-II. In this study, we have investigated the effects of PAX3-FKHR and IGF-II on the expression of muscle regulatory factors (myf5, MyoD and myogenin), and platelet derived growth factor-B (PDGF-B) and vascular endothelial growth factor (VEGF) in mouse C2C12 myoblasts in vitro. PAX3-FKHR induced cell cycling of C2C12 cells and promoted proliferation whilst blocking myogenesis. IGF-II inhibited their differentiation without influencing proliferation. Western blotting showed that PAX3-FKHR and IGF-II blocked the expression of myogenin and MyoD respectively. Since MyoD affects early myogenesis and myogenin controls terminal differentiation, a combination of PAX3-FKHR and IGF-II synergistically blocks myogenesis at several different stages in differentiation. We have also shown that the major survival and angiogenic cytokines, PDGF-B and VEGF, were induced by IGF-II and PAX3-FKHR respectively. A combination of PAX3-FKHR and IGF-II could synergistically up regulate the expression of PDGF-B and VEGF and stabilize their high expression levels. Our results suggest that high expression of PAX3-FKHR and IGF-II in ARMS synergistically play a key role in oncogenesis and tumour progression of ARMS.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
1019-6439
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
27
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1087-96
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pubmed:meshHeading |
pubmed-meshheading:16142327-Animals,
pubmed-meshheading:16142327-Apoptosis,
pubmed-meshheading:16142327-Blotting, Western,
pubmed-meshheading:16142327-Cell Differentiation,
pubmed-meshheading:16142327-Cell Line,
pubmed-meshheading:16142327-Cell Proliferation,
pubmed-meshheading:16142327-Cell Transformation, Neoplastic,
pubmed-meshheading:16142327-Cells, Cultured,
pubmed-meshheading:16142327-Disease Progression,
pubmed-meshheading:16142327-Flow Cytometry,
pubmed-meshheading:16142327-Forkhead Transcription Factors,
pubmed-meshheading:16142327-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:16142327-Insulin-Like Growth Factor II,
pubmed-meshheading:16142327-Mice,
pubmed-meshheading:16142327-Mitosis,
pubmed-meshheading:16142327-Paired Box Transcription Factors,
pubmed-meshheading:16142327-Proto-Oncogene Proteins c-sis,
pubmed-meshheading:16142327-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:16142327-Rhabdomyosarcoma, Alveolar,
pubmed-meshheading:16142327-Time Factors,
pubmed-meshheading:16142327-Transfection,
pubmed-meshheading:16142327-Up-Regulation,
pubmed-meshheading:16142327-Vascular Endothelial Growth Factor A
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pubmed:year |
2005
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pubmed:articleTitle |
The cooperative transforming effects of PAX3-FKHR and IGF-II on mouse myoblasts.
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pubmed:affiliation |
Department of Biological Sciences, Manchester Metropolitan University, Manchester M1 5GD, UK.
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pubmed:publicationType |
Journal Article
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