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

Li, Honggui and Wang, Qiuyu and Li, Hong Mei and Kumar, Shant and Parker, Craig J. and 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.