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.
多药耐药是细胞发生交叉的现象
项目成果
期刊论文数量(0)
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S S THORGEIRSSON其他文献
S S THORGEIRSSON的其他文献
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{{ 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:
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:
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:
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:
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:
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:
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