Abstract
PAX3 or PAX3-FKHR expression is implicated in cell transformation and tumourigenesis. Here, C2C12 myoblasts were transfected with a sense Pax3 vector and a pTet-On system to induce Pax3 expression, whereas to downregulate PAX3-FKHR, Rh18 was transfected with an antisense Pax3 with a pTet-On system. The inhibition of PAX3-FKHR in Rh18 induced upregulation of PTEN. Decreased resistance to apoptosis and increased transformation ability were observed in the Rh18 cells with PAX3-FKHR downregulation. Conversely, Pax3 induction in C2C12 cells downregulated the expression of PTEN and p27(Kip1). These results indicate that the involvement of PAX3 and PAX3-FKHR in rhabdomyosarcoma tumourigenesis may be through downregulation of PTEN tumour suppressor gene, affecting the PTEN/AKT survival pathway.
MeSH terms
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Animals
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Cell Line, Tumor
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Cell Survival / genetics
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Cell Transformation, Neoplastic / genetics*
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Chromatin Immunoprecipitation
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Cyclin-Dependent Kinase Inhibitor p27 / genetics
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Down-Regulation
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Doxycycline / pharmacology
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Gene Expression Regulation, Neoplastic*
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Humans
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Mice
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Neoplasms, Muscle Tissue / genetics*
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Neoplasms, Muscle Tissue / metabolism
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Neoplasms, Muscle Tissue / pathology
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Oncogene Proteins, Fusion / metabolism*
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PAX3 Transcription Factor
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PTEN Phosphohydrolase / genetics*
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Paired Box Transcription Factors / genetics
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Paired Box Transcription Factors / metabolism*
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Promoter Regions, Genetic
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Rhabdomyosarcoma / genetics
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Rhabdomyosarcoma / metabolism
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Rhabdomyosarcoma / pathology*
Substances
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Oncogene Proteins, Fusion
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PAX3 Transcription Factor
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PAX3-FKHR fusion protein, human
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Paired Box Transcription Factors
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Pax3 protein, mouse
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Cyclin-Dependent Kinase Inhibitor p27
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PTEN Phosphohydrolase
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Doxycycline