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GENETIC ANALYSIS OF THE MULTIDRUG RESISTANCE PHENOTYPE IN TUMOR CELLS

GENETIC ANALYSIS OF THE MULTIDRUG RESISTANCE PHENOTYPE IN TUMOR CELLS
肿瘤细胞多药耐药表型的遗传分析
批准号：
3796491
负责人：
I PASTAN
金额：
$0.0万
依托单位：
DIVISION OF CANCER BIOLOGY AND DIAGNOSIS
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
来源：
https://reporter.nih.gov/project-details/3796491
关键词：
P glycoprotein adenosinetriphosphatase bone marrow gene expression genetic transduction human tissue intracellular transport laboratory mouse liposomes membrane permeability molecular cloning multidrug resistance mutant neoplasm /cancer chemotherapy neoplastic cell protein purification tissue /cell culture transfection /expression vector

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英文摘要
Resistance to chemotherapy of human cancers has been studied by establishing in vitro and in vivo genetic systems which mimic development of drug resistance. A major mechanism of multidrug resistance in human cancer is expression of the MDR1 gene which we have cloned and sequenced. Expression of the MDR1 gene carried by retroviral vectors can be used to transduce cells to multidrug resistance and has been used to confer resistance to mouse bone marrow cells in vitro and in vivo. Mechanistic studies on P-glycoprotein suggest that it is involved in removing drug directly from the plasma membrane. To study mechanism, we have generated many mutants and initiated biochemical studies including the purification of P-glycoprotein and reconstruction of drug-dependent ATPase activity in artificial liposomes.
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GENETIC ANALYSIS OF THE MULTIDRUG RESISTANCE PHENOTYPE IN TUMOR CELLS
MONOCLONAL ANTIBODIES TO CANCER CELLS
REGULATION OF GENE ACTIVITY
REGULATION OF GENE ACTIVITY
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