MULTIDRUG RESISTANCE AND PROGRAMMED CELL DEATH IN TUMORIGENESIS
MULTIDRUG RESISTANCE AND PROGRAMMED CELL DEATH IN TUMORIGENESIS
批准号:
3752778
负责人:
S S THORGEIRSSON
金额:
$0.0万
依托单位国家:
美国
项目类别:
财政年份:
--
资助国家:
美国
项目状态:
未结题
起止时间:
至
中文摘要
我们希望研究分子之间可能的联系
耐药的基础和程序性细胞死亡的调节。
在涉及的几种机制中,我们选择比较它们的效果
由于MDR基因的表达与那些由表达引起的
原癌基因bcl2。为了调查可能发生的
我们认为这两种耐药机制之间的相互作用,
作为第一步,要证明在哺乳动物细胞中的表达
最近在我们实验室克隆的大鼠mdr1b基因的
具有MDR表型的患者。作为第二步,我们计划表达
人bcl2基因在含有mdr1b的耐药细胞中的表达
亲本控制细胞系,尝试(1)比较亲缘关系
这些耐药机制的效力,以及(2)看看
它们可以相互协同作用,保护细胞免受
细胞毒剂。第一个目标是通过亚克隆的cDNAs
将大鼠mdr1b基因从pGEM-11Zf()载体克隆到EcoRI酶切位点。
PBK-CMV原核-真核表达载体
巨细胞病毒启动子。PBK-CMV/mdr1b重组载体和pBK-CMV/mdr1b重组载体
然后将载体pBK-CMV单独导入NIH3T3小鼠胚胎
成纤维细胞与脂联胺。Mdr1b赋予的抗性水平
在这些实验中比以前的研究中显示的要高
对转染人MDR1的NIH3T3细胞进行同样的检测
在RSV启动子控制下的基因。因此,NIH/3T3-mdr1b
细胞被认为是比较耐多药的一个很好的模型
具有新的bcl2依赖耐药机制的表型。
英文摘要
We wish to investigate the possible connections between the molecular
basis of drug resistance and the regulation of programmed cell death.
Among several mechanisms involved, we have chosen to compare the effects
due to the expression of mdr genes with those caused by the expression
of the protooncogene bcl-2. In order to investigate the possible
interactions between these two mechanisms of drug resistance we decided,
as a first step, to demonstrate that the expression in mammalian cells
of the rat mdr1b gene, recently cloned in our laboratory, would provide
them with the MDR phenotype. As a second step, we plan to express the
human bcl-2 gene in the resistant cells containing mdr1b and in the
parental control cell line, attempting (1) to compare the relative
potency of these mechanisms of drug resistance, and (2) to see whether
they can act synergistically with each other in protecting cells against
cytotoxic agents. The first goal was achieved by subcloning the cDNA of
the rat mdr1b gene from the pGEM-11Zf(+) plasmid into the EcoRI site of
the pBK-CMV prokaryotic-eukaryotic expression vector, under the control
of the CMV promoter. The pBK-CMV/mdr1b recombinant plasmid and the
vector pBK-CMV alone were then transfected into the NIH3T3 mouse embryo
fibroblasts with lipofectamine. The resistance levels conferred by mdr1b
in these experiments was higher than the one shown in previous studies
by using the same assay on NIH3T3 cells transfected with the human MDR1
gene under the control of the RSV promoter. Therefore, the NIH/3T3-mdr1b
cells are thought to be a good model for comparing the mdr resistant
phenotype with the novel bcl-2 dependent drug-resistant mechanism.
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会议论文
ANALYSIS OF GENETIC ALTERATIONS DURING HEPATOCARCINOGENESIS
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批准号:3774876
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:S S THORGEIRSSON
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依托单位:
HEPATIC STEM CELL COMPARTMENT AND LIVER TUMORS
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批准号:3874676
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:S S THORGEIRSSON
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依托单位:
CLONING OF THE RAT MDR GENE FAMILY AND REGULATION IN NORMAL AND NEOPLASTIC LIVER
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批准号:3853518
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:S S THORGEIRSSON
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依托单位:
ANALYSIS OF CELLULAR AND GENETIC ALTERATIONS DURING HEPATOCARCINOGENESIS
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批准号:3752711
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:S S THORGEIRSSON
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依托单位:
MITOGEN MEDIATED SIGNAL TRANSDUCTION IN CARCINOGENESIS
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批准号:3752738
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:S S THORGEIRSSON
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依托单位:
CELL SURFACE PROTEINS AND CELLULAR ADHESION IN HEPATOCARCINOGENESIS
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批准号:3963469
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:S S THORGEIRSSON
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依托单位:
TRANSGENIC MODELS--COOPERATION OF C MYC AND GROWTH FACTORS IN TUMORIGENESIS
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批准号:5201568
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:S S THORGEIRSSON
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依托单位:
CELLULAR AND MOLECULAR BIOLOGY OF THE HEPATIC STEM CELL COMPARTMENT
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批准号:3774824
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:S S THORGEIRSSON
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依托单位:
POLYPEPTIDE MODULATION IN MCF-7 CELLS BY ESTROGEN AND GROWTH FACTORS
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批准号:3939733
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:S S THORGEIRSSON
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依托单位:
GENETIC DETERMINANTS IN CHEMICAL HEPATOCARCINOGENESIS
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批准号:3916835
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:S S THORGEIRSSON
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依托单位:
CELLULAR PROTEINS IN ONCOGENE TRANSFORMED RAT LIVER EPITHELIAL CELLS
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批准号:3916909
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:S S THORGEIRSSON
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依托单位:
POLYPEPTIDE MODULATION IN MCF-7 CELLS BY ESTROGEN AND GROWTH FACTORS
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批准号:3916861
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:S S THORGEIRSSON
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依托单位:
CELLULAR POLYPEPTIDES ASSOCIATED WITH METASTASIS OF RAT MAMMARY TUMOR CELLS
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批准号:3916862
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:S S THORGEIRSSON
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依托单位:
TRANSGENIC MODELS--COOPERATION OF ONCOGENES AND GROWTH FACTORS IN TUMORIGENESIS
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批准号:3752769
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:S S THORGEIRSSON
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依托单位:
CELLULAR AND MOLECULAR BIOLOGY OF THE HEPATIC STEM CELL COMPARTMENT
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批准号:3838377
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:S S THORGEIRSSON
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依托单位:
CELLULAR AND MOLECULAR BIOLOGY OF THE HEPATIC STEM CELL COMPARTMENT
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批准号:3853463
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:S S THORGEIRSSON
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依托单位:
NEGATIVE GROWTH REGULATORS IN NORMAL AND NEOPLASTIC LIVER
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批准号:3853493
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:S S THORGEIRSSON
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依托单位:
CELLULAR POLYPEPTIDES ASSOCIATED WITH METASTASIS OF RAT MAMMARY TUMOR CELLS
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批准号:3939734
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:S S THORGEIRSSON
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依托单位:
INITIATION AND TERMINATION OF HEPATOCYTE PROLIFERATION BY SERUM FACTORS
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批准号:3963535
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:S S THORGEIRSSON
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依托单位:
CHEMICAL TRANSFORMATION OF HUMAN LYMPHOBLASTOID CELL LINES
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批准号:3963543
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:S S THORGEIRSSON
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依托单位: