Mutation in TSC2 and activation of mammalian target of rapamycin signalling pathway in renal angiomyolipoma
Mutation in TSC2 and activation of mammalian target of rapamycin signalling pathway in renal angiomyolipoma
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DOI：
10.1016/s0140-6736(03)13044-9
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发表时间：
2003-04-19
期刊：
影响因子：
168.9
通讯作者：
Kwiatkowski, DJ
中科院分区：
文献类型：
--
作者：
El-Hashemite, N;Zhang, HB;Kwiatkowski, DJ
使 TSC1 或 TSC2 失活的突变会导致结节性硬化症。我们使用免疫印迹和免疫组织化学分析来观察结节性硬化症中发生的血管平滑肌脂肪瘤中 p70 S6 激酶和核糖体 S6 蛋白是否存在磷酸化。 Hamartin（由 TSC1 编码）和 S6K 在所有样品中均表达。马铃薯蛋白 (TSC2) 在血管平滑肌脂肪瘤中较弱或不存在，但存在于健康肾脏中，而磷酸化 p70 S6 激酶和 p56 仅存在于血管平滑肌脂肪瘤中。我们的结果表明结节性硬化症病变中雷帕霉素代谢途径的哺乳动物靶标被激活，这有助于其生长。我们建议雷帕霉素及其类似物的治疗可能使此类患者受益。
Mutations that inactivate either TSC1 or TSC2 cause tuberous sclerosis. We have used immunoblotting and immunohistochemical analysis to see whether there is phosphorylation of p70 S6 kinase, and the ribosomal S6 protein in anglomyolipomas occurring in tuberous sclerosis. Hamartin (encoded by TSC1) and S6K was expressed in all samples. Tuberin (TSC2) was weak or absent in angiomyolipomas, but present in healthy kidney, whereas, phosphorylated p70 S6 kinase and p56 were present only in angiomyolipomas. Our results indicate activation of a mammalian target of rapamycin metabolic pathway in tuberous sclerosis lesions, which contributes to their growth. We suggest that treatment with rapamycin and its analogues could benefit such patients.