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

Li, Honggui, Wang, Qiuyu, Li, Hong Mei, Kumar, Shant, Parker, Craig J., Slevin, Mark and Kumar, Patricia (2007) PAX3 and PAX3-FKHR promote rhabdomyosarcoma cell survival through downregulation of PTEN. Cancer letters, 253 (2). pp. 215-23. ISSN 0304-3835

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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.