GENETIC ANALYSIS OF MULTIDRUG RESISTANCE GENES

对药物的耐药性的发展是对药物的主要限制。 用化疗成功治疗恶性肿瘤。 多药 耐药（MDR），定义为对一种以上耐药的肿瘤 毒品，尤其是问题。 MDR部分原因是 P-糖蛋白/MDR基因的过度表达。 这些基因的功能是 腺苷三磷酸（ATP）依赖性转运蛋白，可以挤出一个 从细胞中释放大量疏水化合物。 正常 人类MDR基因的功能尚不清楚;然而，它们是 超家族的膜结合转运分子，ATP结合 ABC超家族。 在大肠杆菌中，至少有25个ABC基因 已经被鉴定出来，而在人类中只有8个基因成员 超家族已经被描述。 人类ABC基因参与了几个 囊性纤维化和肾上腺脑白质营养不良等疾病。 为了 为了表征新的人类ABC基因，我们筛选了表达的 序列标签数据库，并确定了几个新的序列， 代表ABC基因。 到目前为止，四个克隆，含有序列的 这些基因是ABC超家族的成员。 四 基因在序列和表达模式上显示出广泛的多样性。 此外，使用体细胞杂交板绘制的新基因， 荧光原位杂交，位于染色体1，9和 10;在与先前绘制的该基因的基因不同的位置， 超家族 在不同肿瘤中的表达研究正在进行中， 最终目的是对所述基因进行功能表征。 此外，ABC基因的遗传特征可能揭示了 许多功能上重要的分子，可能涉及在 通过细胞运输物质。

The development of resistance to drugs is a major limitation to the successful treatment of malignancies with chemotherapy. Multidrug resistance (MDR), defined as tumors that are resistant to more than one drug, is particularly problematic. MDR is partially due to the overexpression of the P-glycoprotein/MDR genes. These genes function as adenosine triphosphate (ATP)-dependent transporters that can extrude a large variety of hydrophobic compounds from the cell. The normal function of the human MDR genes is unknown; however, they are part of a super-family of membrane-bound transport molecules, the ATP-binding cassette (ABC) superfamily. In Escherichia coli at least 25 ABC genes have been identified, whereas in humans only 8 members of the gene superfamily have been described. Human ABC genes are involved in several diseases such as cystic fibrosis and adrenoleuko-dystrophy. In an effort to characterize new human ABC genes, we have screened the expressed sequence tags database and identified several new sequences that may represent ABC genes. To date four clones, containing sequences of the genes that are members of the ABC superfamily, were identified. The four genes display extensive diversity in sequence and expression pattern. In addition, the new genes, mapped using somatic cell hybrid panels and fluorescence in situ hybridization, are located on chromosomes 1, 9 and 10; at locations distinct from previously mapped genes of this superfamily. Expression studies in different tumors are in progress, the ultimate goal being a functional characterization of the described genes. Furthermore, genetic characterization of the ABC genes may reveal a number of functionally important molecules that may be involved in the transport of substances by cells.