| Summary: | 碩士 === 國立中央大學 === 生命科學研究所 === 97 === Alveolar rhabdomyosarcoma is the most frequently detected malignant solid tumor in children and is associated with the translocated chimeric genes PAX3-, and Pax7- FoxO1. These chimeric proteins have potent transforming effects and are inhibitors of myogenic differentiation; thus it suggests that FoxO1 should play important roles in myogenesis. Recent studies have shown that over-expression of FoxO1 caused muscular atrophy and reduced type I fibers. To further elucidate the roles of FoxO1 in myogenesis, we examined the effects of FoxO1 over-expression on myogenic terminal differentiation, and we found that the effect was inhibitory. Subsequently, we like to identify the pathways mediating this effect to test whether they can rescue FoxO1 mediating inhibition of myogenesis. Luckly, we found that both insulin and LiCl could rescue FoxO1 inhibited myogenesis and their effects were synergistic. Another surprise was that we found p38 pathway can restore C2C12-FoxO1-H215R myoblasts insulin induced terminal differentiation. In the future, we will investigate whether LiCl and Wnt-3a treatment trigger the translocation of FoxO1 from nucleus.
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