Lincke C R, Broeks A, The I, Plasterk R H, Borst P
Laboratory of Biochemistry, University of Amsterdam, The Netherlands.
EMBO J. 1993 Apr;12(4):1615-20. doi: 10.1002/j.1460-2075.1993.tb05806.x.
P-glycoproteins can cause multidrug resistance in mammalian tumor cells by active extrusion of cytotoxic drugs. The natural function of these evolutionarily conserved, membrane-bound ATP binding transport proteins is unknown. In mammals, P-glycoproteins are abundantly present in organs associated with the digestive tract. We have studied the tissue-specific expression of Caenorhabditis elegans P-glycoprotein genes pgp-1 and pgp-3 by transformation of nematodes with pgp-lacZ gene fusion constructs in which the promoter area of the pgp genes was fused to the coding region of lacZ. Expression of pgp-1 and pgp-3, as inferred from pgp-lacZ transgenic nematodes, was confined to the intestinal cells. The expression patterns of both genes were virtually indistinguishable. Quantitative analysis of pgp mRNA levels during development showed that pgp-1, -2, and -3 were expressed throughout the life cycle of C.elegans, albeit with some variation indicating developmental regulation. The expression of P-glycoprotein genes in intestinal cells is an evolutionarily conserved feature of these genes, consistent with the hypothesis that P-glycoproteins provide a mechanism of protection against environmental toxins.
P-糖蛋白可通过主动排出细胞毒性药物,导致哺乳动物肿瘤细胞产生多药耐药性。这些在进化上保守的膜结合ATP结合转运蛋白的天然功能尚不清楚。在哺乳动物中,P-糖蛋白大量存在于与消化道相关的器官中。我们通过用pgp-lacZ基因融合构建体转化线虫,研究了秀丽隐杆线虫P-糖蛋白基因pgp-1和pgp-3的组织特异性表达,其中pgp基因的启动子区域与lacZ的编码区域融合。从pgp-lacZ转基因线虫推断,pgp-1和pgp-3的表达局限于肠道细胞。这两个基因的表达模式几乎没有区别。发育过程中pgp mRNA水平的定量分析表明,pgp-1、-2和-3在秀丽隐杆线虫的整个生命周期中均有表达,尽管存在一些变化表明有发育调控。P-糖蛋白基因在肠道细胞中的表达是这些基因在进化上保守的特征,这与P-糖蛋白提供一种抵御环境毒素机制的假设一致。