PAX3 and PAX3-FKHR promote rhabdomyosarcoma cell survival through downregulation of PTEN

• Published in: Cancer letters Vol. 253; no. 2; pp. 215 - 223
• Main Authors: Li, Hong Gui, Wang, Qiuyu, Li, Hong Mei, Kumar, Shant, Parker, Craig, Slevin, Mark, Kumar, Patricia
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 18.08.2007; Elsevier Limited
• Subjects: Animals; Cell growth; Cell Line, Tumor; Cell Survival - genetics; Cell Transformation, Neoplastic - genetics; Chromatin Immunoprecipitation; Cyclin-Dependent Kinase Inhibitor p27 - genetics; Down-Regulation; Doxycycline - pharmacology; Gene Expression Regulation, Neoplastic; Genes; Hematology, Oncology and Palliative Medicine; Humans; Kinases; Mice; Neoplasms, Muscle Tissue - genetics; Neoplasms, Muscle Tissue - metabolism; Neoplasms, Muscle Tissue - pathology; Oncogene Proteins, Fusion - metabolism; Paired Box Transcription Factors - genetics; Paired Box Transcription Factors - metabolism; PAX3; PAX3 Transcription Factor; PAX3-FKHR; Promoter Regions, Genetic; PTEN; PTEN Phosphohydrolase - genetics; Rhabdomyosarcoma; Rhabdomyosarcoma - genetics; Rhabdomyosarcoma - metabolism; Rhabdomyosarcoma - pathology; Rodents; Studies; PTEN; PAX3; PAX3-FKHR; Rhabdomyosarcoma
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2007.01.020

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 p27Kip1 . 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.