Mutations of the Smad2 and Smad4 genes in lung adenocarcinomas induced by N‐nitrosobis(2‐hydroxypropyl)amine in rats-猫眼课题宝

N-亚硝基双(2-羟丙基)胺诱导大鼠肺腺癌中Smad2和Smad4基因突变

DOI：

发表时间：

2000

期刊：

Molecular Carcinogenesis

影响因子：

4.6

通讯作者：

中科院分区：

医学2区

文献类型：

作者：

T. Tsujiuchi;Y. Sasaki;M. Tsutsumi;Y. Konishi

在大鼠中研究了N-亚硝基双（2-羟丙基）胺（BHP）诱导的肺腺癌中Smad 2和Smad 4基因的突变，这些基因被鉴定为转化生长因子β途径的介质。6周龄雄性Wistar大鼠在饮用水中给予2000 ppm BHP，持续12周，并保持不进行额外处理，直至第25周处死。从12例腺癌中提取总RNA，通过逆转录-聚合酶链反应限制性单链构象多态性分析和测序分析研究Smad 2和Smad 4的突变。在Smad 2中，单个腺癌在密码子100处显示GGC到GAC（Gly到Asp）的转变，在密码子383处显示AAG到GAG（Lys到Glu）的转变。在Smad 4中，一个腺癌在密码子214处表现出TTC到CTC（Phe到Leu）的转变。这些结果表明，Smad 2和Smad 4的突变可能在BHP诱导的大鼠肺腺癌的有限部分中发挥作用。摩尔巨蟹座29：87-91，2000.© 2000 Wiley利斯公司

Mutations of the Smad2 and Smad4 genes, identified as mediators of the transforming growth factor‐β pathway, were investigated in lung adenocarcinomas induced by N‐nitrosobis(2‐hydroxypropyl)amine (BHP) in rats. Male Wistar rats, 6 wk old, were given 2000 ppm BHP in their drinking water for 12 wk and maintained without additional treatment until killed at week 25. Total RNA was extracted from 12 adenocarcinomas, and mutations in Smad2 and Smad4 were investigated by reverse transcription–polymerase chain reaction restriction single‐strand conformation polymorphism analysis followed by sequencing analysis. In Smad2, single adenocarcinomas showed a GGC to GAC (Gly to Asp) transition at codon 100 and an AAG to GAG (Lys to Glu) transition at codon 383. In Smad4, one adenocarcinoma exhibited a TTC to CTC (Phe to Leu) transition at codon 214. These results suggest that mutations of Smad2 and Smad4 may play roles in a limited fraction of lung adenocarcinomas induced by BHP in rats. Mol. Carcinog. 29:87–91, 2000. © 2000 Wiley‐Liss, Inc.

Mammalian dwarfins are phosphorylated in response to transforming growth factor beta and are implicated in control of cell growth.