Sequencing of the rat beta-catenin gene (Ctnnb1) and mutational analysis of liver tumors induced by 2-amino-3-methylimidazo[4,5-f]quinoline.
Sequencing of the rat beta-catenin gene (Ctnnb1) and mutational analysis of liver tumors induced by 2-amino-3-methylimidazo[4,5-f]quinoline.
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大鼠β-连环蛋白基因（Ctnnb1）的测序和2-氨基-3-甲基咪唑[4,5-f]喹啉诱导的肝肿瘤的突变分析。
DOI：
10.1016/s0378-1119(01)00839-3
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发表时间：
2002
期刊：
影响因子：
3.5
通讯作者：
Dashwood,RoderickH
中科院分区：
文献类型：
--
作者：
Li,Qingjie;Dixon,BrianM;Al-Fageeh,Mohamed;Blum,CarmenA;Dashwood,RoderickH
β-连环蛋白是一种在钙粘附素介导的细胞间黏附和信号转导中发挥作用的蛋白质，由于其在多种人类癌症中的作用，近年来受到越来越多的关注。人β-连环蛋白基因(CTNNB1)的初级序列已知一段时间，而大鼠β-连环蛋白基因(CTNNB1)的初级序列迄今尚未得到详细研究。我们在这里报告了CTNNB1的一级结构，使用基于PCR的方法和直接测序。CTNNB1基因全长为9082bp。我们发现大鼠CTNNB1基因包含14个外显子，大小从61到356个核苷酸，13个内含子，大小从76到2524个核苷酸。转录起始点位于位于外显子1的ATG密码子上游157bp处，转录本全长2650个核苷酸(编码781个氨基酸的蛋白质)。我们发现5‘非编码区由157个核苷酸组成，3’非编码区长147个核苷酸。大鼠CTNNB1的糖原合成酶-3β结构域编码区域位于β的第二外显子，而人类CTNNB1的编码区域位于第三外显子。根据对初级序列的最新了解，我们对十几个2-氨基-3-甲基咪唑并[4，5-f]喹啉(IQ)诱导的大鼠肝肿瘤进行了筛查，以确定其全部14个外显子是否存在突变。令人惊讶的是，没有发现突变。这些结果是在IQ诱导的β-连环蛋白突变的器官特异性的背景下讨论的，这种突变在结肠癌中非常普遍，但在肝脏肿瘤中很少见。
β-Catenin, a protein that functions in cadherin-mediated cell–cell adhesion as well as in signal transduction, has received increasing attention in recent years due to its role as an oncogene in various human cancers. The primary sequence of the human β-catenin gene (CTNNB1) has been known for some time, but that of the rat β-catenin gene (Ctnnb1) has not heretofore been studied in detail. We report here the primary structure of Ctnnb1 using PCR-based methods and direct sequencing. The size of the complete Ctnnb1 gene was determined to be 9082 bp. We found the rat Ctnnb1 gene to contain 14 exons, ranging in size from 61 to 356 bp, and 13 introns ranging in size from 76 to 2524 bp. The transcription start site appears to be 157 bp upstream of the ATG codon located in exon 1. The resulting transcript is 2650 nucleotides long (encoding a protein of 781 amino acids). We found the 5′ UTR to consist of 157 nucleotides and the 3′ UTR to be 147 nucleotides long. The region coding for the glycogen synthase kinase-3β domain of β-catenin is located in exon 2 of rat Ctnnb1, in contrast to human CTNNB1 in which it is found in exon 3. Based on the newly acquired knowledge of the primary sequence, more than a dozen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ)-induced rat liver tumors were screened for the presence or absence of mutations in all 14 exons of rat Ctnnb1. Surprisingly, no mutations were found. The results are discussed in the context of the organ-specificity of IQ-induced mutations in β-catenin, being highly prevalent in colon tumors, but much less common in liver tumors.
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DOI：
10.1073/pnas.85.23.8998
发表时间：
1988-12-01
影响因子：
11.1
作者：
FROHMAN, MA;DUSH, MK;MARTIN, GR
通讯作者：
MARTIN, GR
影响因子：
4.7
作者：
Blum, CA;Xu, MR;Dashwood, RH
通讯作者：
Dashwood, RH
给予 1,2-二甲基肼或 2-氨基-3-甲基-咪唑的大鼠中叶绿素和吲哚-3-甲醇的后引发效应。
影响因子：
4.7
作者：
Xu,M;Orner,GA;Bailey,GS;Stoner,GD;Horio,DT;Dashwood,RH
通讯作者：
Dashwood,RH
小肠癌的分子和生物学分析：涉及外显子 3 的间质缺失导致 β-catenin 基因突变和复制错误表型
影响因子：
9.8
作者：
M. Murata;K. Iwao;Y. Miyoshi;Y. Nagasawa;T. Ohta;Kunitaka Shibata;K. Oda;H. Wada;S. Tominaga;Yasuki Matsuda;M. Ohsawa;Yusuke Nakamura;T. Shimano
通讯作者：
T. Shimano
F344 大鼠中两种杂环胺诱导的结肠肿瘤中出现高频率的 β-连环蛋白 (ctnnb1) 突变。
影响因子：
11.2
作者：
Dashwood,RH;Suzui,M;Nakagama,H;Sugimura,T;Nagao,M
通讯作者：
Nagao,M