Alternative splice variant of actinin-4 in small cell lung cancer
Alternative splice variant of actinin-4 in small cell lung cancer
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DOI：
10.1038/sj.onc.1207652
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发表时间：
2004-07-01
期刊：
影响因子：
8
通讯作者：
Hirohashi, S
中科院分区：
文献类型：
--
作者：
Honda, K;Yamada, T;Hirohashi, S
肿瘤相关的选择性RNA剪接已经得到了相当大的关注。我们在人小细胞肺癌(SCLC)中发现了一个新的Actinin-4选择性剪接变异体RNA。剪接变异体的表达在小细胞肺癌细胞系(10/10)、活检组织(3/3)和睾丸组织中高度特异。该变异体编码一个外显子8有三个氨基酸变化的多肽，其中胚系错义突变发生在家族性局灶性节段性肾小球硬化(FSGS)中。该变异体蛋白与丝状肌动蛋白聚合物有很高的亲和力，不与皮质肌动蛋白结合。另外，剪接的肌动蛋白-4可能是一种新的小细胞肺癌诊断标记物和选择性治疗的候选靶点。
Tumor-associated alternative RNA splicing has gained considerable attention. We identified a novel alternative splice variant RNA of actinin-4 in human small cell lung caner (SCLC). Expression of the splice variant was highly specific to SCLC cell lines (10/10), biopsies (3/3), and testis. The variant encoded a peptide with a three amino-acid change in exon 8, where the germline missense mutation takes place in familial focal segmental glomerulosclerosis (FSGS). The variant protein showed high affinity to filamentous actin polymers and was not localized with cortical actin. Alternatively spliced actinin-4 may be a new diagnostic marker of SCLC and a candidate target for selective therapy.