GENETIC ANALYSIS OF MULTIDRUG RESISTANCE GENES

多药耐药(MDR)，定义为肿瘤对广泛的 药物的谱系，是癌症化疗的一大限制。MDR输入 至少部分细胞是由于P-糖蛋白过度表达所致 (Pgp)/mdr基因。PGP是三磷酸腺苷家族的一员 (ATP)依赖的转运体，并已被证明导致外流 从细胞中提取的多种化合物。该基因家族被称为 三磷酸腺苷结合盒(ABC)家族及其成员运输 生物膜上的各种化合物。人类的ABC基因是 参与了包括囊性纤维化在内的多种疾病， 肾上腺脑白质营养不良与家族性持续性高胰岛素血症 低血糖症。最近，一种名为mrp的基因被鉴定为 在耐多药的肺肿瘤细胞中过表达，并似乎 成为药物-谷胱甘肽结合物的运输者。MRP也是成员 ABC运输机家族的成员。以确定新的基因参与了 我们已经确定和表征了获得多药耐药性的情况 来自不同组织的新的MDR和MRP相关基因。在……里面 此外，我们还克隆了人类秀丽线虫的同源物。 并打乱该基因，建立了研究MRP的模型系统 功能。本项目的目标是探索这些角色 正常和恶性细胞中的基因，并开发模型系统 研究它们的功能。

Multidrug resistance (MDR), defined as the resistance of tumors to a wide spectrum of drugs, is a major limitation of cancer chemotherapy. MDR in at least some cells is due to the overexpression of the P-glycoprotein (PGP)/MDR gene. PGP is a member of a family of adenosine triphosphate (ATP)- dependent transporters and has been shown to cause the efflux of a large variety of compounds from the cell. The gene family is known as the ATP-binding cassette (ABC) family, and its members transport multiple diverse compounds across biological membranes. Human ABC genes are involved in a number of diseases including cystic fibrosis, adrenoleukodystrophy, and familial persistent hyperinsulinemic hypoglycemia. Recently a gene, termed MRP, was identified as being overexpressed in a multidrug-resistant lung tumor cell, and appears to be a transporter for drug-glutathione conjugates. MRP is also a member of the ABC family of transporters. To identify new genes involved in the attainment of multidrug resistance we have identified and characterized new MDR and MRP-related genes from several different tissues. In addition, we have cloned a Caenorhabditis elegans homolog of the human MRP gene and disrupted this gene to develop a model system to study MRP function. The objective of this project is to explore the role of these genes in normal and malignant cells, and to develop model systems to study their function.