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 pgpl 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 pgpl 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.Tumors that become resistant to antineoplastic drugs often render cancer chemotherapy ineffective (13). Cell lines selected for resistance in vitro to a single cytotoxic drug have been used to study the molecular mechanism of this phenomenon. These cell lines are also cross-resistant to a wide range of structurally and functionally unrelated drugs, and their patterns of cross-resistance are complex and variable, depending on the drugs used for selection (13). The basis of multidrug resistance (MDR) appears to be reduced net cellular accumulation of drugs resulting from an energydependent increase in drug efflux (5,20,33).Overproduction of a 170,000-dalton membrane glycoprotein termed P-glycoprotein is intimately associated with expression of the MDR phenotype (21-23). Transfection experiments (8,16,36) have demonstrated that overproduction of P-glycoprotein is sufficient to cause MDR. Analyses of partial and full-length cDNAs encoding P-glycoprotein from hamster (11,12), mouse (15,17), and human (3, 37; A. M. van der Bliek, P. M. Kooiman, C. Schneider, and P. Borst, Gene, in press) cells have shown that P-glycoprotein is a highly conserved protein which appears to be tandemly duplicated. Each duplicated half consists of six potential membrane-spanning regions and a putative nucleotidebinding site, features compatible with the proposed role of P-glycoprotein as an energy-dependent pump (3,12,15). The highest level of amino acid sequence homology occurs in the cytoplasmic domains encompassing the nucleotide-binding sites and the C-terminal domain (17, 37). Each half of the protein also has a high degree of primary amino acid sequence and structural homology with bacterial transport proteins, particularly hemolysin B (12), suggesting that they evolved independently from a common ancestral gene.A family of closely related genes, referred to as ...

Background: Oil palm is the second largest source of edible oil which contributes to approximately 20% of the world's production of oils and fats. In order to understand the molecular biology involved in in vitro propagation, flowering, efficient utilization of nitrogen sources and root diseases, we have initiated an expressed sequence tag (EST) analysis on oil palm.

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.