CLONING OF THE RAT MDR GENE FAMILY AND REGULATION IN NORMAL AND NEOPLASTIC LIVER
大鼠 MDR 基因家族的克隆及其在正常和肿瘤肝脏中的调节
基本信息
- 批准号:3853518
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:
- 资助国家:美国
- 起止时间:至
- 项目状态:未结题
- 来源:
- 关键词:
项目摘要
Multidrug resistance is the phenomenon by which cells become cross-
resistant to a range of unrelated compounds in response to exposure to a
single agent; this resistance is the result of overexpression of a 170 Kd
membrane protein, p-glycoprotein, which is encoded by the mdr gene(s).
Previously, we have shown that exposure of rats to xenobiotic agents such
as the carcinogens aflatoxin B1, isosafrole and 2-acetylaminofluorene
(2-AAF) causes increased expression of mdr mRNA in the liver. To further
study the mechanism by which xenobiotics regulate mdr gene expression, we
have employed a primary hepatocyte culture system. Exposure of isolated
hepatocytes to methycholanthrene (MC), 2-AAF but not 2,3,7,8 -
tetrachlorodibenzo-p-dioxin (TCDD) increased the expression of mdr mRNA
expression; concomitant increases in cytochrome P4501A gene(s) expression
were also observed with these agents. Inhibition of protein synthesis
also increased the expression of mdr mRNA in these cells. The enhanced
mdr expression caused by these compounds is a result of increased
transcription. These data suggest that mdr expression is regulated by a
protein that is distinct from the Ah receptor. To further investigate
the mechanism of mdr regulation it was necessary to isolate the rat mdr
genes. We have identified that the rat mdr gene family is comprised of
three members; one of these genes has been isolated and characterized.
Sequence analysis of a complete cDNA for a rat mdr cDNA indicated a high
degree of identity to the mouse mdrlb gene (mdrl); thus, this rat cDNA
was designated the mdrlb gene. Further studies on the 5' promoter and
possible 3' mRNA stability regions are being performed. We observed in
normal liver a slight but significant zonal difference of distribution of
mdr transcripts (zone 1 > zone 3). Significant increase of mdr
transcripts during regeneration was observed mainly in zone 1
hepatocytes. Our data suggest that the increased mdr expression might
represent a subpopulation of preneoplastic nodules which possibly
undergoes malignant transformation more specifically than GST-P positive
nodules.
多药耐药是细胞交叉耐药的现象。
对一系列不相关的化合物有抗性,
单剂;这种耐药性是170 Kd的过度表达的结果。
膜蛋白,p-糖蛋白,其由MDR基因编码。
以前,我们已经表明,大鼠暴露于外源性物质,
作为致癌物的黄曲霉毒素B1、异黄樟油素和2-乙酰氨基芴
(2-AAF)引起肝脏mdr mRNA表达增加。 进一步
为了研究外源性物质调控mdr基因表达的机制,
采用了原代肝细胞培养系统。 隔离的暴露
肝细胞对甲基胆蒽(MC)、2-AAF,但对2,3,7,8-
四氯二苯并二恶英(TCDD)可增加mdr mRNA的表达
表达;细胞色素P4501 A基因表达伴随增加
也观察到了这些药物。 抑制蛋白质合成
并增加mdr mRNA的表达。 增强的
由这些化合物引起的MDR表达是由于增加的
转录。 这些数据表明,mdr的表达是由一个
与Ah受体不同的蛋白质。 为了进一步研究
MDR的调控机制有必要分离大鼠MDR
基因. 我们已经确定大鼠mdr基因家族由以下组成:
三个成员;其中一个基因已被分离和表征。
对大鼠mdr cDNA的完整cDNA序列分析表明,
与小鼠mdrlb基因(mdrl)的同一性程度;因此,该大鼠cDNA
被命名为mdrlb基因。 对5'启动子和
可能的3 ′ mRNA稳定区正在进行。 我们观察到
正常肝组织中,
MDR转录物(区1 >区3)。 MDR显著增加
再生过程中的转录本主要在第1区观察到
肝细胞 我们的数据表明,mdr表达的增加可能
代表了一个肿瘤前结节的亚群,
恶性转化比GST-P阳性更特异
结节
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 }}
S S THORGEIRSSON其他文献
S S THORGEIRSSON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('S S THORGEIRSSON', 18)}}的其他基金
ANALYSIS OF GENETIC ALTERATIONS DURING HEPATOCARCINOGENESIS
肝癌发生过程中的基因改变分析
- 批准号:
3774876 - 财政年份:
- 资助金额:
-- - 项目类别:
CELLULAR AND MOLECULAR BIOLOGY OF THE HEPATIC STEM CELL COMPARTMENT
肝干细胞区室的细胞和分子生物学
- 批准号:
3774824 - 财政年份:
- 资助金额:
-- - 项目类别:
ANALYSIS OF CELLULAR AND GENETIC ALTERATIONS DURING HEPATOCARCINOGENESIS
肝癌发生过程中的细胞和基因改变分析
- 批准号:
3752711 - 财政年份:
- 资助金额:
-- - 项目类别:
MULTIDRUG RESISTANCE AND PROGRAMMED CELL DEATH IN TUMORIGENESIS
肿瘤发生中的多药耐药性和程序性细胞死亡
- 批准号:
3752778 - 财政年份:
- 资助金额:
-- - 项目类别:
TRANSGENIC MODELS--COOPERATION OF C MYC AND GROWTH FACTORS IN TUMORIGENESIS
转基因模型--C MYC和生长因子在肿瘤发生中的合作
- 批准号:
5201568 - 财政年份:
- 资助金额:
-- - 项目类别:
POLYPEPTIDE MODULATION IN MCF-7 CELLS BY ESTROGEN AND GROWTH FACTORS
雌激素和生长因子对 MCF-7 细胞中多肽的调节
- 批准号:
3939733 - 财政年份:
- 资助金额:
-- - 项目类别:
CELL SURFACE PROTEINS AND CELLULAR ADHESION IN HEPATOCARCINOGENESIS
肝癌发生中的细胞表面蛋白和细胞粘附
- 批准号:
3963469 - 财政年份:
- 资助金额:
-- - 项目类别:
相似海外基金
Molecular and pathological understanding of oral early cancer using mouse chemical carcinogenesis model
使用小鼠化学致癌模型对口腔早期癌的分子和病理学理解
- 批准号:
17K11609 - 财政年份:2017
- 资助金额:
-- - 项目类别:
Grant-in-Aid for Scientific Research (C)
PP6 as a tumor suppressor in mouse two-stage chemical carcinogenesis
PP6 作为小鼠两阶段化学致癌过程中的肿瘤抑制因子
- 批准号:
15K10081 - 财政年份:2015
- 资助金额:
-- - 项目类别:
Grant-in-Aid for Scientific Research (C)
Role of local P450 enzymes in chemical carcinogenesis in mouse mammary gland
局部P450酶在小鼠乳腺化学癌变中的作用
- 批准号:
7870588 - 财政年份:2010
- 资助金额:
-- - 项目类别:
Effects of radiation exposure of adolescents on chemical carcinogenesis
青少年辐射暴露对化学致癌的影响
- 批准号:
22610026 - 财政年份:2010
- 资助金额:
-- - 项目类别:
Grant-in-Aid for Scientific Research (C)
Role of local P450 enzymes in chemical carcinogenesis in mouse mammary gland
局部P450酶在小鼠乳腺化学癌变中的作用
- 批准号:
8063627 - 财政年份:2010
- 资助金额:
-- - 项目类别:
Possibility of prevention with crude drugs or Kampo medicine on chemical carcinogenesis
用生药或汉方药预防化学癌的可能性
- 批准号:
20590010 - 财政年份:2008
- 资助金额:
-- - 项目类别:
Grant-in-Aid for Scientific Research (C)
Immunofluorescence imaging analysis for intra- and inter-cellular signal transduction mechanisms in chemical carcinogenesis models
化学致癌模型中细胞内和细胞间信号转导机制的免疫荧光成像分析
- 批准号:
20510071 - 财政年份:2008
- 资助金额:
-- - 项目类别:
Grant-in-Aid for Scientific Research (C)
BRIN: URI: TMSR/CHEMICAL CARCINOGENESIS SUBCORE
BRIN:URI:TMSR/化学致癌子核心
- 批准号:
6973513 - 财政年份:2004
- 资助金额:
-- - 项目类别: