Role of Ki-ras in the Pathogenesis of Lung Cancer
Ki-ras 在肺癌发病机制中的作用
基本信息
- 批准号:6467967
- 负责人:
- 金额:$ 31.42万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2002
- 资助国家:美国
- 起止时间:2002-04-01 至 2006-03-30
- 项目状态:已结题
- 来源:
- 关键词:alleles carcinogens environment related neoplasm /cancer gene expression gene mutation genetic regulation genetic strain genetically modified animals laboratory mouse laser capture microdissection lung neoplasms neoplasm /cancer genetics neoplastic process oncoprotein p21 pathologic process polymerase chain reaction tobacco transfection tumor suppressor genes
项目摘要
DESCRIPTION (provided by applicant): Studies in humans and animal models have
shown that mutation of Ki-ras is a critical, early event in lung tumorigenesis.
We and others have shown that the type of mutation present in Ki-ras may
influence tumor progression and appears to correlate with patient survival. We
thus hypothesize that different mutations induced in Ki-ras by environmental
carcinogens exhibit different oncogenic potential, and that the type of
mutation initially induced in this gene will determine how rapidly tumors
progress to adenocarcinomas. It is difficult to definitively determine the role
of mutated ras genes in tumor initiation and progression because treatment with
chemical carcinogens may cause alterations at other genetic loci. We thus
propose to develop 3 strains of transgenic mice that contain either the wild
type, VAL12, or CYS12 mutant alleles of the human Ki-ras gene linked to a
tet-inducible promoter that specifies lung specific expression of the
transgene. The biochemical characteristics and activity of the 3 alleles will
be compared and correlated with the oncogenicity of each allele.
Carcinogenicity bioassays will be employed to determine the effects of
different ras mutations on tumor development and progression. The effect of
each of the 3 alleles on subsequent damage to tumor suppressor loci implicated
in both human and murine lung tumor pathogenesis, in particular the pl6Ink4a,
Rb, and cyclin D1 genes, will be assessed by PCR-SSCP, methylation specific
PCR, and determination of the levels of expression of the gene products by
reverse transcription PCR. The development of these "humanized" Ki-ras
transgenic mice will represent a critical advance in this field and provide an
important new research tool that will allow us to determine the role of Ki-ras
mutations in the pathogenesis of lung cancer. We anticipate that the proposed
studies will elucidate the effect of different mutant ras alleles on lung tumor
pathogenesis and will have important long term implications for future research
on the etiology, genetics, prevention, and development of novel therapies for
lung cancer.
描述(申请人提供):对人体和动物模型的研究
研究表明,Ki-ras基因突变在肺癌发生中是一个关键的早期事件。
我们和其他人已经表明,Ki-ras中存在的突变类型可能
影响肿瘤进展,并似乎与患者的生存相关。我们
从而假设环境诱导Ki-ras基因的不同突变
致癌物质表现出不同的致癌潜力,并且类型
该基因最初诱导的突变将决定肿瘤发生的速度
腺癌的进展。很难明确地确定这一角色
突变的ras基因在肿瘤发生和发展中的作用
化学致癌物可能会导致其他基因位点的改变。因此,我们
建议开发3个品系的转基因小鼠,这些小鼠要么含有野生的
人Ki-ras基因的类型、VAL12或CyS12突变等位基因与
Tet可诱导启动子,指定肺组织特异性表达
转基因。这3个等位基因的生化特征和活性将
与每个等位基因的致瘤性进行比较和关联。
致癌性生物测定将被用来确定
不同ras基因突变在肿瘤发生发展中的作用。的影响
3个等位基因中的每一个都与肿瘤抑制基因的后续损伤有关
在人类和小鼠肺肿瘤的发病机制中,尤其是pl6Ink4a,
Rb和细胞周期蛋白D1基因将通过甲基化特异性的PCR-SSCP进行评估
聚合酶链式反应,检测基因产物的表达水平
逆转录-聚合酶链式反应。这些“人性化”基拉的发展
转基因小鼠将代表着这一领域的关键进步,并提供
重要的新研究工具,将使我们能够确定Ki-ras的作用
肺癌发病机制中的突变。我们预计,拟议的
研究将阐明不同突变的ras等位基因对肺癌的影响。
发病机制,并将对未来的研究具有重要的长期意义
关于糖尿病的病因、遗传学、预防和新疗法的开发
肺癌。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
MARK Steven MILLER其他文献
MARK Steven MILLER的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('MARK Steven MILLER', 18)}}的其他基金
SINGLE SKELETAL MUSCLE FIBER MECHANICS AND MYOSIN KINETICS IN HUMAN AGING
人类衰老过程中的单骨骼肌纤维力学和肌球蛋白动力学
- 批准号:
8166995 - 财政年份:2010
- 资助金额:
$ 31.42万 - 项目类别:
SINGLE SKELETAL MUSCLE FIBER MECHANICS AND MYOSIN KINETICS IN HUMAN AGING
人类衰老过程中的单骨骼肌纤维力学和肌球蛋白动力学
- 批准号:
8168640 - 财政年份:2010
- 资助金额:
$ 31.42万 - 项目类别:
FINITE ELEMENT ANALYSIS OF FEMORAL INTRAMEDULLARY NAIL INSERTION
股骨髓内钉置入的有限元分析
- 批准号:
7956281 - 财政年份:2009
- 资助金额:
$ 31.42万 - 项目类别:
FINITE ELEMENT ANALYSIS OF FEMORAL INTRAMEDULLARY NAIL INSERTION
股骨髓内钉置入的有限元分析
- 批准号:
7723422 - 财政年份:2008
- 资助金额:
$ 31.42万 - 项目类别:
TERAGRID: THE ENCYCLOPEDIA OF LIFE: A NOVEL TOOLKIT FOR ENABLING HIGH THROUGHPU
TERAGRID:生命百科全书:实现高吞吐量的新型工具包
- 批准号:
7181788 - 财政年份:2004
- 资助金额:
$ 31.42万 - 项目类别:
Role of Ki-ras in the Pathogenesis of Lung Cancer
Ki-ras 在肺癌发病机制中的作用
- 批准号:
6867387 - 财政年份:2002
- 资助金额:
$ 31.42万 - 项目类别:
Role of Ki-ras in the Pathogenesis of Lung Cancer
Ki-ras 在肺癌发病机制中的作用
- 批准号:
6872830 - 财政年份:2002
- 资助金额:
$ 31.42万 - 项目类别:
Role of Ki-ras in the Pathogenesis of Lung Cancer
Ki-ras 在肺癌发病机制中的作用
- 批准号:
6730470 - 财政年份:2002
- 资助金额:
$ 31.42万 - 项目类别:
Role of Ki-ras in the Pathogenesis of Lung Cancer
Ki-ras 在肺癌发病机制中的作用
- 批准号:
6730654 - 财政年份:2002
- 资助金额:
$ 31.42万 - 项目类别:
Role of Ki-ras in the Pathogenesis of Lung Cancer
Ki-ras 在肺癌发病机制中的作用
- 批准号:
7030175 - 财政年份:2002
- 资助金额:
$ 31.42万 - 项目类别:
相似海外基金
New strategy for preventing colorectal cancer by targeting polyamines, which are thought to be carcinogens
通过针对被认为是致癌物质的多胺来预防结直肠癌的新策略
- 批准号:
23K17454 - 财政年份:2023
- 资助金额:
$ 31.42万 - 项目类别:
Grant-in-Aid for Challenging Research (Pioneering)
CMA-Basic and Translational Mechanisms of Cancer Initiation of the Urothelium in Veterans Exposed to Carcinogens: Interception of tobacco smoking-related bladder cancer by an epigenetic approach
CMA-暴露于致癌物的退伍军人尿路上皮癌症发生的基本和转化机制:通过表观遗传学方法拦截与吸烟相关的膀胱癌
- 批准号:
10260302 - 财政年份:2022
- 资助金额:
$ 31.42万 - 项目类别:
Environmental Carcinogens Induce Minority MOMP to Initiate Carcinogenesis in Lung Cancer and Mesothelioma whileMaintaining Apoptotic Resistance via Mcl-1
环境致癌物诱导少数 MOMP 引发肺癌和间皮瘤的癌变,同时通过 Mcl-1 维持细胞凋亡抵抗
- 批准号:
10356565 - 财政年份:2022
- 资助金额:
$ 31.42万 - 项目类别:
BCCMA: Basic and Translational Mechanisms of Cancer Initiation of the Urothelium in Veterans Exposed to Carcinogens: Role of PPARg in theFormation and Progression of Carcinoma in situ of the Bladder
BCCMA:暴露于致癌物的退伍军人尿路上皮癌症发生的基本和转化机制:PPARg 在膀胱原位癌形成和进展中的作用
- 批准号:
10361590 - 财政年份:2022
- 资助金额:
$ 31.42万 - 项目类别:
BCCMA: Basic and Translational Mechanisms of Cancer Initiation of the Urothelium in Veterans Exposed to Carcinogens: Role of PPARg in theFormation and Progression of Carcinoma in situ of the Bladder
BCCMA:暴露于致癌物的退伍军人尿路上皮癌症发生的基本和转化机制:PPARg 在膀胱原位癌形成和进展中的作用
- 批准号:
10616472 - 财政年份:2022
- 资助金额:
$ 31.42万 - 项目类别:
CMA-Basic and Translational Mechanisms of Cancer Initiation of the Urothelium in Veterans Exposed to Carcinogens: Interception of tobacco smoking-related bladder cancer by an epigenetic approach
CMA-暴露于致癌物的退伍军人尿路上皮癌症发生的基本和转化机制:通过表观遗传学方法拦截与吸烟相关的膀胱癌
- 批准号:
10647629 - 财政年份:2022
- 资助金额:
$ 31.42万 - 项目类别:
Occupational Exposures of Firefighters to Combustion-derived Mutagens and Carcinogens
消防员因职业接触燃烧衍生诱变剂和致癌物
- 批准号:
547881-2020 - 财政年份:2022
- 资助金额:
$ 31.42万 - 项目类别:
Postgraduate Scholarships - Doctoral
Environmental Carcinogens Induce Minority MOMP to Initiate Carcinogenesis in Lung Cancer and Mesothelioma whileMaintaining Apoptotic Resistance via Mcl-1
环境致癌物诱导少数 MOMP 引发肺癌和间皮瘤的癌变,同时通过 Mcl-1 维持细胞凋亡抵抗
- 批准号:
10543157 - 财政年份:2022
- 资助金额:
$ 31.42万 - 项目类别:
BCCMA: Basic and Translational Mechanisms of Cancer Initiation of the Urothelium in Veterans Exposed to Carcinogens: Defining the Molecular and Spatial Features of Carcinoma in situ of the Bladder
BCCMA:暴露于致癌物的退伍军人尿路上皮癌症发生的基本和转化机制:定义膀胱原位癌的分子和空间特征
- 批准号:
10513321 - 财政年份:2021
- 资助金额:
$ 31.42万 - 项目类别:
BCCMA: Basic and Translational Mechanisms of Cancer Initiation of the Urothelium in Veterans Exposed to Carcinogens: Leveraging Artificial Neural Networks to Enhance Detection of Carcinoma in situ
BCCMA:暴露于致癌物的退伍军人尿路上皮癌症发生的基本和转化机制:利用人工神经网络增强原位癌的检测
- 批准号:
10260145 - 财政年份:2021
- 资助金额:
$ 31.42万 - 项目类别: