Mutation Analysis of Human Cytokeratin 8 Gene in Malignant Rhabdoid Tumor: A Possible Association with Intracytoplasmic Inclusion Body Formation
Mutation Analysis of Human Cytokeratin 8 Gene in Malignant Rhabdoid Tumor: A Possible Association with Intracytoplasmic Inclusion Body Formation
复制标题
恶性横纹肌样瘤中人细胞角蛋白8基因突变分析：与胞浆内包涵体形成的可能关联
作者：
H. Shiratsuchi;Tsuyoshi Saito;A. Sakamoto;E. Itakura;S. Tamiya;Y. Oshiro;Y. Oda;S. Toh;S. Komiyama;M. Tsuneyoshi
横纹肌样细胞通常见于恶性横纹肌样瘤(MRT)和其他恶性肿瘤，具有嗜酸性细胞质，内含球形核周包涵体。这种独特的细胞在许多类型的恶性肿瘤中被认为是高度侵袭性的指示物，其特征是中间丝聚集，包括波形蛋白和细胞角蛋白(CK)8，主要表达于简单类型的上皮，如肝脏和肠道。为了阐明包涵体形成的原因，我们用逆转录聚合酶链式反应和直接测序的方法分析了7份MRT标本(3份来自冷冻材料，4份来自培养细胞系)中人CK8基因全长(KRT 8：1724碱基对)的变化。此外，对缺乏横纹肌样特征的两个细胞系HuH7和HeLa，6例儿童恶性肿瘤，包括3例原始神经外胚层肿瘤(PNET)和3例Wilms瘤，以及15例正常肝组织(作为对照)也进行了分析。所有MRT标本均存在Krt8基因错义突变，分别为Arg89→Cys(5/7)、Arg→Cys251(3/7)、Glu267→Lys(6/7)、Ser290→Ile，Met；(7/7)和Arg301→His(4/7)。在这些突变中，最值得注意的发现是Arg89属于头部结构域的H1亚域，Arg251属于短的非螺旋连接片段，或L1-2。这两个突变都以与侧向原丝-原丝相互作用的关系而闻名。此外，Ser290是一个磷酸化位点，被认为在细丝组织中发挥重要作用，导致CK8微丝的构象变化。综上所述，MRT的CK8基因突变密码子位于参与中间丝构象变化的重要区域。
The rhabdoid cell, which is typically observed in malignant rhabdoid tumor (MRT) and other malignant neoplasms, has an eosinophilic cytoplasm containing a spheroid perinuclear inclusion body. This distinct cell is known to act as a highly aggressive indicator in many types of malignant tumors and is characterized by aggregates of intermediate filaments, comprising both vimentin and cytokeratin (CK) 8, which is mainly expressed in simple-type epithelium such as liver and intestine. To clarify the cause of the inclusion body formation, we analyzed the alteration of the complete human CK8 gene (KRT 8: 1724 base pairs) in seven samples of MRT (three from frozen materials and four from cultured cell lines) by reverse-transcriptase polymerase chain reaction, followed by direct sequencing. In addition, the two cell lines, Huh7 and HeLa, which lacked rhabdoid feature, six pediatric malignant tumors, including three cases of primitive neuroectodermal tumor (PNET) and three of Wilms' tumor; and 15 normal liver tissue (as a control) were also analyzed. All MRT samples had missense mutations in the human KRT 8 gene, i.e., Arg89 → Cys (5/7); Arg → Cys251 (3/7); Glu267 → Lys (6/7); Ser290 → Ile, Met; (7/7) and Arg301 → His(4/7), none of which was detected in any control samples. Among these mutations, the most noteworthy findings were that Arg89 belongs to the H1 subdomain of the head domain and that Arg251 belongs to the short nonhelical linker segment, or L1–2. Both these mutations are noted for their relationships to lateral protofilament–protofilament interactions. In addition, Ser290 has been previously reported to be a phosphorylation site, which has been recognized to play an important role in filament organization, leading to conformational change of the CK8 filaments. In conclusion, mutated codons of CK8 gene in MRT were located in the important region involved in the conformational change of intermediate filament.
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DOI：
10.1073/pnas.90.15.7414
发表时间：
1993-08-01
影响因子：
11.1
作者：
CHAN, YM;YU, QC;FUCHS, E
通讯作者：
FUCHS, E
影响因子：
15.9
作者：
Ku, NO;Michie, SA;Omary, MB
通讯作者：
Omary, MB
人胎盘细胞角蛋白 cDNA 的克隆和序列 8. cAMP 对滋养层细胞 mRNA 的调节。
DOI：
10.1210/mend-4-3-370
发表时间：
1990
期刊：
Molecular endocrinology (Baltimore, Md.)
影响因子：
--
作者：
Yamamoto,R;Kao,LC;McKnight,CE;Strauss3rd,JF
通讯作者：
Strauss3rd,JF
Weber-Cockayne 单纯性大疱性表皮松解症患者角蛋白 5 的非螺旋连接片段 L1-2 突变。
影响因子：
4
作者：
Chan,YM;Yu,QC;LeBlanc-Straceski,J;Christiano,A;Pulkkinen,L;Kucherlapati,RS;Uitto,J;Fuchs,E
通讯作者：
Fuchs,E