Ng W F, Sarangi F, Zastawny R L, Veinot-Drebot L, Ling V
Ontario Cancer Institute, Canada.
Mol Cell Biol. 1989 Mar;9(3):1224-32. doi: 10.1128/mcb.9.3.1224-1232.1989.
Overproduction of P-glycoprotein is intimately associated with multidrug resistance. This protein appears to be encoded by a multigene family. Thus, differential expression of different members of this family may contribute to the complexity of the multidrug resistance phenotype. Three lambda genomic clones isolated from a hamster genomic library represent different members of the hamster P-glycoprotein gene family. Using a highly conserved exon probe, we found that the hamster P-glycoprotein gene family consists of three genes. We also found that the P-glycoprotein gene family consists of three genes in mice but has only two genes in humans and rhesus monkeys. The hamster P-glycoprotein genes have similar exon-intron organizations within the 3' region encoding the cytoplasmic domains. We propose that the hamster P-glycoprotein gene family arose from gene duplication. The hamster pgp1 and pgp2 genes appear to be more closely related to each other than either gene is to the pgp3 gene. We speculate that the hamster pgp1 and pgp2 genes arose from a recent gene duplication event and that primates did not undergo this duplication and therefore contain only two P-glycoprotein genes.
P-糖蛋白的过度产生与多药耐药密切相关。这种蛋白质似乎由一个多基因家族编码。因此，该家族不同成员的差异表达可能导致多药耐药表型的复杂性。从仓鼠基因组文库中分离出的三个λ基因组克隆代表了仓鼠P-糖蛋白基因家族的不同成员。使用高度保守的外显子探针，我们发现仓鼠P-糖蛋白基因家族由三个基因组成。我们还发现小鼠的P-糖蛋白基因家族由三个基因组成，但人类和恒河猴中只有两个基因。仓鼠P-糖蛋白基因在编码细胞质结构域的3'区域内具有相似的外显子-内含子组织。我们提出仓鼠P-糖蛋白基因家族起源于基因复制。仓鼠pgp1和pgp2基因彼此之间的关系似乎比任何一个基因与pgp3基因的关系都更密切。我们推测仓鼠pgp1和pgp2基因起源于最近的一次基因复制事件，而灵长类动物没有经历这次复制，因此只含有两个P-糖蛋白基因。
