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Mutation and Expression Analyses of Cycin-Dependent Kinase Inhibitor Gene, p571KIP2 in Childhood Malignant Solid Tumors

细胞周期蛋白依赖性激酶抑制剂基因 p571KIP2 在儿童恶性肿瘤中的突变和表达分析

基本信息

批准号：
09671830
负责人：
FUKUZAWA Masahiro
金额：
$ 1.98万
依托单位：
Nihon University (1998)Osaka University (1997)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09671830/
关键词：
p57 KIP2 neuroblastoma Wilms' tumor hepatoblastoma Rliabdomyosarcoma 横紋筋肉腫

项目摘要

Purpose Mammalian cyclin-dependent kinase inhibitors consist of two families, the p16 family and the p21 family. These proteins are all capable of inhibiting progression of the cell cycle by binding and inhibiting GィイD21ィエD2 cyclin/cyclin-dependent kinase complexes. The p16 gene was isolated from 9p21, a chromosomal region that is a common site for loss of heterozygosity in many tumors, and found to be mutated and homozygously deleted in many types of tumors. Therefore, p16 is regarded as one of the tumor suppressor genes. On the other hand, p57 is a member of the p21 family, and the gene encoding p57 is located at 11p15.5. This region is also a common site fur loss of heterozygosity in many tumors, especially childhood tumors including Wilms' tumor, hepatoblastoma and rhabdomyosarcoma. In the current study, the author performed a mutational analysis of the p16 gene and investigated mRNA expression of the p16 and p57 genes in a variety of childhood malignant solid tumors.Methods : Mutational analysis was done by using polymerase chain reaction-single-strand conformation polymorphism method, and for mRNA expression analyses, semi-quantitative reverse transcription polymerase chain reaction method was used.Results : Among 111 tumors analyzed, no malignancy associated mutation was detected. However, reduced expression of the p16 gene was found in 42% (5/12) of the Wilms' tumors and 40% (4/10) of the rhabdomyosarcomas. Moreover, reduced expression of the p57 gene was also observed in 14%(2/14)of the neuroblastomas, 21% (3/14) of the hepatoblastomas, 25% (3/12) of the Wilms' tumors, and 30% (3/19) of the rhabdomyosarcomas.Conclusions : Our data may indicate that the reduced expression of seine cyclin-dependent kinase inhibitors has a role in the pathogenesis of childhood malignant solid tumors.

目的哺乳动物周期蛋白依赖性激酶抑制剂包括两个家族，p16家族和p21家族。这些蛋白都能够通过结合和抑制细胞周期蛋白/细胞周期蛋白依赖性激酶复合物来抑制细胞周期的进展。p16基因是从染色体9p21中分离出来的，9p21是许多肿瘤中常见的杂合性缺失位点，在许多类型的肿瘤中发现突变和纯合性缺失。因此，p16被认为是肿瘤抑制基因之一。另一方面，p57是p21家族的成员，编码p57的基因位于11p15.5。该区域也是许多肿瘤中杂合性缺失的常见部位，尤其是儿童肿瘤，包括Wilms肿瘤、肝母细胞瘤和横纹肌肉瘤。在本研究中，作者对p16基因进行了突变分析，并研究了p16和p57基因在多种儿童恶性实体瘤中的mRNA表达。方法：采用聚合酶链反应-单链构象多态性法进行突变分析，采用半定量反转录聚合酶链反应法进行mRNA表达分析。结果：在所分析的111例肿瘤中，未检出恶性相关突变。然而，p16基因在42%（5/12）的Wilms肿瘤和40%（4/10）的横纹肌肉瘤中表达降低。此外，14%（2/14）的神经母细胞瘤、21%（3/14）的肝母细胞瘤、25%（3/12）的肾母细胞瘤和30%（3/19）的横纹肌肉瘤中p57基因的表达也有所降低。结论：我们的数据可能表明，seine细胞周期蛋白依赖性激酶抑制剂的表达降低在儿童恶性实体瘤的发病机制中起作用。