GENETIC ANALYSIS OF MULTIDRUG RESISTANCE GENES

多药耐药（MDR）是指肿瘤对多种化疗药物的耐药性。 药物谱，是癌症化疗的主要限制。 多药耐药 至少某些细胞是由于P-糖蛋白的过度表达 (PGP)/MDR基因。 PGP是三磷酸腺苷家族的成员 （ATP）依赖性转运蛋白，并已被证明可引起外排 从细胞中释放出各种各样的化合物 基因家族被称为 ATP结合盒（ABC）家族及其成员转运多种 不同的化合物穿过生物膜。 人类ABC基因 与许多疾病有关，包括囊性纤维化， 肾上腺脑白质营养不良和家族性持续性高胰岛素血症 低血糖 最近，一种名为MRP的基因被鉴定为 在多药耐药肺肿瘤细胞中过度表达， 是药物-谷胱甘肽结合物的转运体。 MRP也是会员 ABC运输机家族的成员 为了确定参与这些基因的新基因， 我们已经发现并描述了 新的MDR和MRP相关基因从几个不同的组织。 在 此外，我们还克隆了一个秀丽隐杆线虫的人类同源物， MRP基因，并破坏该基因，以建立一个模型系统，研究MRP 功能 本项目的目的是探讨这些作用， 正常和恶性细胞中的基因，并开发模型系统， 研究其功能。

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.