Uterus Hyperplasia and Increased Carcinogen-Induced Tumorigenesis in Mice Carrying a Targeted Mutation of the Chk2 Phosphorylation Site in Brca1

Sang Soo Kim; Liu Cao; Cuiling Li; Xiaoling Xu; L. Julie Huber; Lewis A. Chodosh; Chu-Xia Deng

首页> 外文期刊>Molecular and Cellular Biology >Uterus Hyperplasia and Increased Carcinogen-Induced Tumorigenesis in Mice Carrying a Targeted Mutation of the Chk2 Phosphorylation Site in Brca1

【24h】

Uterus Hyperplasia and Increased Carcinogen-Induced Tumorigenesis in Mice Carrying a Targeted Mutation of the Chk2 Phosphorylation Site in Brca1

机译：携带Brca1的Chk2磷酸化位点的目标突变的小鼠子宫增生和致癌物诱导的肿瘤发生。

获取原文

掌桥外文数据库（机构版） >>

开具论文收录证明 >>

文献代查 >>

页面导航

摘要
著录项
相似文献
相关主题

摘要

The tumor suppressor BRCA1 contains multiple functional domains that interact with many proteins. After DNA damage, BRCA1 is phosphorylated by CHK2 at serine 988, followed by a change in its intracellular location. To study the functions of CHK2-dependent phosphorylation of BRCA1, we generated a mouse model carrying the mutation S971A (S971 in mouse Brca1 corresponds to S988 in human BRCA1) by gene targeting. Brca1S971A/S971A mice were born at the expected ratio without a developmental defect, unlike previously reported Brca1 mutant mice. However, Brca1S971A/S971A mice suffered a moderately increased risk of spontaneous tumor formation, with a majority of females developing uterus hyperplasia and ovarian abnormalities by 2 years of age. After treatment with DNA-damaging agents, Brca1S971A/S971A mice exhibited several abnormalities, including increased body weight, abnormal hair growth pattern, lymphoma, mammary tumors, and endometrial tumors. In addition, the onset of tumor formation became accelerated, and 80% of the mutant mice had developed tumors by 1 year of age. We demonstrated that the Brca1S971A/S971A cells displayed reduced ability to activate the G₂/M cell cycle checkpoint upon γ-irradiation and to stabilize p53 following N-methyl-N′-nitro-N-nitrosoguanidine treatment. These observations suggest that Chk2 phosphorylation of S971 is involved in Brca1 function in modulating the DNA damage response and repressing tumor formation.

机译：肿瘤抑制物BRCA1包含与许多蛋白质相互作用的多个功能域。 DNA损伤后，BRCA1在CHK2的丝氨酸988处被磷酸化，随后其细胞内位置发生变化。为了研究BRCA1的依赖CHK2的磷酸化功能，我们通过基因靶向产生了携带突变S971A（小鼠Brca1中的S971对应人BRCA1中的S988）的小鼠模型。与以前报道的Brca1突变小鼠不同， Brca1 S971A / S971A 小鼠以预期的比例出生，没有发育缺陷。但是， Brca1 S971A / S971A 小鼠自发性肿瘤形成的风险适度增加，大多数雌性到2岁时会出现子宫增生和卵巢异常。用DNA损伤剂治疗后， Brca1 S971A / S971A 小鼠表现出一些异常，包括体重增加，毛发生长异常，淋巴瘤，乳腺肿瘤和子宫内膜肿瘤。另外，肿瘤形成的发作变得加速，并且80％的突变小鼠到1岁已经发展成肿瘤。我们证明了 Brca1 S971A / S971A 细胞在γ射线照射后激活G _{2 / M细胞周期检查点并稳定的能力降低n N -甲基- N '-硝基- N -亚硝基胍处理后的p53。这些观察结果表明，S971的Chk2磷酸化参与了调节DNA损伤反应并抑制肿瘤形成的Brca1功能。} 展开▼

著录项

来源
《Molecular and Cellular Biology》 |2004年第21期|共10页

作者
Sang Soo Kim; Liu Cao; Cuiling Li; Xiaoling Xu; L. Julie Huber; Lewis A. Chodosh; Chu-Xia Deng;
展开▼

作者单位

展开▼

收录信息

原文格式 PDF

正文语种

中图分类细胞生物学;

关键词

相似文献

外文文献

中文文献

专利

1. Impaired skin and mammary gland development and increased gamma-irradiation-induced tumorigenesis in mice carrying a mutation of S1152-ATM phosphorylation site in Brca1. [J] . Kim SS, Cao L, Baek H Cancer research: The official organ of the American Association for Cancer Research, Inc . 2009,第24期

机译：在携带Brca1中S1152-ATM磷酸化位点突变的小鼠中，皮肤和乳腺发育受损，γ辐射诱导的肿瘤发生增加。

2. Impaired skin and mammary gland development and increased gamma-irradiation-induced tumorigenesis in mice carrying a mutation of S1152-ATM phosphorylation site in Brca1. [J] . Kim SS, Cao L, Baek H Cancer research: The official organ of the American Association for Cancer Research, Inc . 2009,第24期

机译：在携带Brca1中S1152-ATM磷酸化位点突变的小鼠中，皮肤和乳腺发育受损，γ辐射诱导的肿瘤发生增加。

3. Absence of full-length Brca1 sensitizes mice to oxidative stress and carcinogen-induced tumorigenesis in the esophagus and forestomach [J] . Liu Cao Xiaoling Xu Longyue L. Cao Rui-Hong Wang Xavier Coumoul Sang S. Kim1 and Chu-Xia Deng Carcinogenesis . 2007,第7期

机译：缺乏全长Brca1使小鼠对食管和前胃癌中的氧化应激和致癌物诱导的肿瘤发生敏感

4. Identification of Phosphorylation Sites in Chk2 Kinase [C] . Henry W. Rohrs, Ilan Geerlof-Vidavsky, Manolo D. Plasencia, American Society for Mass Spectrometry Conference on Mass Spectrometry and Allied Topics . 2013

机译：CHK2激酶中磷酸化位点的鉴定

5. Analysis of Mice Carrying Human GNAO1 Mutations as a Model to Study Associated Movement Disorders [D] . Larrivee, Casandra Lynn 2019

机译：携带人类GNAO1突变的小鼠的分析作为研究相关运动障碍的模型

6. Uterus Hyperplasia and Increased Carcinogen-Induced Tumorigenesis in Mice Carrying a Targeted Mutation of the Chk2 Phosphorylation Site in Brca1 [O] . Sang Soo Kim, Liu Cao, Cuiling Li, 2004

机译：携带Brca1的Chk2磷酸化位点的目标突变的小鼠子宫增生和致癌物诱导的肿瘤发生。

7. Uterus Hyperplasia and Increased Carcinogen-Induced Tumorigenesis in Mice Carrying a Targeted Mutation of the Chk2 Phosphorylation Site in Brca1 [O] . Kim, Sang Soo, Cao, Liu, Li, Cuiling, 2004

机译：携带Brca1的Chk2磷酸化位点的目标突变的小鼠子宫增生和致癌物诱导的肿瘤发生。

1. 血管扩张刺激磷蛋白的磷酸化位点突变对PDGF-BB诱导细胞迁移的影响 [J] . 张亚辉 ,张德玲 ,欧阳静萍 . 中国病理生理杂志 . 2010,第001期

2. JWA编码区PKC磷酸化位点突变对佛波酯诱导MCF-7细胞分化的影响 [J] . 叶健 ,李爱萍 ,秋雯 . 中华劳动卫生职业病杂志 . 2007,第007期

3. 胆囊切除术后患肠癌的机制/抗CD22重组免疫毒素BL22治疗对化疗有耐药性的毛状细胞性白血病的效果/BRCA1 or BRCA2突变携带者及非携带者的产次、口服避孕药和患卵巢癌危险的相关性 [J] . . 中华医学信息导报 . 2001,第019期

4. BRCA1基因能阻断两种性激素——BRCA1基因突变女性易患乳腺癌、宫颈癌和子宫内膜癌得到解释 [J] . 聆风（摘译） . 中华医学信息导报 . 2006,第004期

5. 携带ND1基因G3635A突变的Leber遗传性视神经病变三家系线粒体基因突变位点检测及其分子遗传致病机制 [J] . 赵福新 ,周翔天 ,张永梅 . 中华眼底病杂志 . 2011,第005期

6. DNA损伤剂对携带BRCA1功能位点突变细胞的毒性作用研究 [C] . 罗月 ,董超 ,赵锡鹏 . 第十三届全国劳动卫生与职业病学术会议 . 2014

7. 孤儿受体TR3通过Chk2磷酸化参与顺铂诱导的细胞凋亡抑制肠道肿瘤发生 [A] . 姚路明 . 2011

1. 一种用于人类BRCA1和BRCA2基因全编码序列突变位点检测的引物、方法和试剂盒 [P] . 中国专利： CN109402257A . 2019-03-01

2. 检测人类BRCA1和BRCA2基因全外显子序列突变位点的方法和引物 [P] . 中国专利： CN104531862B . 2017.12.29

3. METHOD FOR INDUCING SITE-SPECIFIC RNA MUTATIONS, TARGET EDITING GUIDE RNA USED IN METHOD, AND TARGET RNA TARGET EDITING GUIDE RNA COMPLEX [P] . 外国专利： EP3323890A4 . 2019-01-30

机译：诱导特定位点RNA突变的方法，该方法中使用的目标编辑指南RNA和目标RNA目标编辑指南RNA复合物

4. METHOD FOR INDUCING SITE-SPECIFIC RNA MUTATIONS, TARGET EDITING GUIDE RNA USED IN METHOD, AND TARGET RNA TARGET EDITING GUIDE RNA COMPLEX [P] . 外国专利： EP3323890A1 . 2018-05-23

机译：诱导特定位点RNA突变的方法，该方法中使用的目标编辑指南RNA和目标RNA目标编辑指南RNA复合物

5. METHOD FOR INDUCING SITE-SPECIFIC RNA MUTATIONS, TARGET EDITING GUIDE RNA USED IN METHOD, AND TARGET RNA–TARGET EDITING GUIDE RNA COMPLEX [P] . 外国专利： WO2017010556A1 . 2017-01-19

机译：诱导特定于站点的RNA突变的方法，该方法中使用的目标编辑指南RNA以及目标RNA-目标编辑指南RNA复合体

相关主题

Uterus Hyperplasia and Increased Carcinogen-Induced Tumorigenesis in Mice Carrying a Targeted Mutation of the Chk2 Phosphorylation Site in Brca1

摘要

著录项

相似文献

相关主题

期刊订阅