title: PAX3 and PAX3-FKHR promote rhabdomyosarcoma cell survival through downregulation of PTEN.
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.
authors.affiliation: School of Biology, Chemistry and Health Science, Manchester Metropolitan University, Manchester M1 5GD, United Kingdom.
authors.forename: Hong Gui
authors.initials: HG
authors.lastname: Li
authors.forename: Qiuyu
authors.initials: Q
authors.lastname: Wang
authors.forename: Hong Mei
authors.initials: HM
authors.lastname: Li
authors.forename: Shant
authors.initials: S
authors.lastname: Kumar
authors.forename: Craig
authors.initials: C
authors.lastname: Parker
authors.forename: Mark
authors.initials: M
authors.lastname: Slevin
authors.forename: Patricia
authors.initials: P
authors.lastname: Kumar
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D047369:Chromatin Immunoprecipitation; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics; D015536:Down-Regulation; D004318:Doxycycline / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D009379:Neoplasms, Muscle Tissue / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015514:Oncogene Proteins, Fusion / Q000378:metabolism*; D000072041:PAX3 Transcription Factor; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012208:Rhabdomyosarcoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
chemical_list: D015514:Oncogene Proteins, Fusion; D000072041:PAX3 Transcription Factor; C523321:PAX3-FKHR fusion protein, human; D051761:Paired Box Transcription Factors; C068686:Pax3 protein, mouse; D050760:Cyclin-Dependent Kinase Inhibitor p27; D051059:PTEN Phosphohydrolase; D004318:Doxycycline