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目的探讨转化生长因子β1(TGF β1)信号转导通路中TGF β1、受体(TβR Ⅰ、TβRⅡ)及胞内转导分子(Smad2、Smad4)在横纹肌肉瘤(rhabdomyosarcoma,RMS)中的表达,及其在肿瘤发生发展中可能的作用机制。方法 应用免疫组织化学技术(S-P法)及TR-PCR分别检测石蜡包埋人体横纹肌肉瘤组织及横纹肌肉瘤细胞株RD中TGF β1信号转导通路中各成分的蛋白及mRNA表达水平,与正常骨骼肌组织和成肌细胞(Myoblasts,Mb)比较。结果 在横纹肌肉瘤石蜡组织中TGF β1、Smad2和Smad4的高表达率分别为58.6％(41／70)、70％(49／70)和75.7％(53／70),对应正常骨骼肌组织的高表达率分别为28％(7／25)、24％(6／25)和28％(7／25)。两组间都有明显差异(P<0.01)。TβR Ⅰ、TβR Ⅱ在RMS及正常骨骼肌组织中普遍表达,两组无明显差异(P>0.05)。TGF β1、TGF βR Ⅰ、TGF βRⅡ、Smad2和Smad4 mRNA水平在RD细胞株中都明显高于正常成肌细胞.结论 RMS中存在TGF β1自分泌现象.Smad2、Smad4介导了TGF β1信号从细胞表面受体到细胞核内的转导。TGF β1信号转导途径可能参与了横纹肌肉瘤的发生与发展。
Objective To investigate the expression of TGFβ1, TβR Ⅰ, TβRⅡ and Smad2 in rhabdomyosarcoma (RMS) and TGFβ1 signaling pathway Its possible role in the development of tumor mechanism. Methods Immunohistochemistry (SP method) and TR-PCR were used to detect the protein and mRNA expression levels of TGFβ1 signal transduction pathway in rhabdomyosarcoma tissues and rhabdomyosarcoma cell lines RD, respectively, and normal skeletal muscle Tissue and myoblasts (Myoblasts, Mb) comparison. Results The high expression rates of TGF β1, Smad2 and Smad4 in paraffin tissues of rhabdomyosarcoma were 58.6% (41/70), 70% (49/70) and 75.7% (53/70) respectively, corresponding to the high normal skeletal muscle tissue The expression rates were 28% (7/25), 24% (6/25) and 28% (7/25), respectively. There was a significant difference between the two groups (P <0.01). TβR Ⅰ and TβR Ⅱ were universally expressed in RMS and normal skeletal muscle tissues, with no significant difference between the two groups (P> 0.05). TGFβ1, TGFβRⅠ, TGFβRⅡ, Smad2 and Smad4 mRNA levels were significantly higher than normal myoblasts in RD cell lines.Conclusion TGFβ1 autocrine exists in RMS.Smad2 and Smad4 mediate the expression of TGFβ1 signaling from cells Transduction of surface receptors into the nucleus. TGF β1 signal transduction pathway may be involved in the occurrence and development of rhabdomyosarcoma.