Li Hong Gui, Wang Qiuyu, Li Hong Mei, Kumar Shant, Parker Craig, Slevin Mark, Kumar Patricia
School of Biology, Chemistry and Health Science, Manchester Metropolitan University, Manchester M1 5GD, United Kingdom.
Cancer Lett. 2007 Aug 18;253(2):215-23. doi: 10.1016/j.canlet.2007.01.020. Epub 2007 Mar 9.
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.
PAX3 或 PAX3-FKHR 的表达与细胞转化和肿瘤发生有关。在此，用正义 Pax3 载体和 pTet-On 系统转染 C2C12 成肌细胞以诱导 Pax3 表达，而用反义 Pax3 和 pTet-On 系统转染 Rh18 以下调 PAX3-FKHR。Rh18 中 PAX3-FKHR 的抑制诱导了 PTEN 的上调。在 PAX3-FKHR 下调的 Rh18 细胞中观察到对凋亡的抗性降低和转化能力增强。相反，C2C12 细胞中 Pax3 的诱导下调了 PTEN 和 p27(Kip1)的表达。这些结果表明，PAX3 和 PAX3-FKHR 在横纹肌肉瘤肿瘤发生中的作用可能是通过下调 PTEN 肿瘤抑制基因，影响 PTEN/AKT 生存途径。
