Identification of members of the P-glycoprotein multigene family.

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.

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Amplification of the P-Glycoprotein Gene Family and Multidrug Resistance

Gene Amplification in Mammalian Cells ◽

10.1201/9781003066989-26 ◽

2020 ◽

pp. 287-300

Author(s):

Lela Veinot ◽

Victor Ling

Keyword(s):

Multidrug Resistance ◽

Gene Family ◽

Glycoprotein Gene ◽

P Glycoprotein

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Changes in the nature of P-glycoprotein gene transcripts during the development of multidrug resistance in CHO cells.

Cell Biology International ◽

10.1006/cbir.1995.1005 ◽

1995 ◽

Vol 19 (1) ◽

pp. 35-42 ◽

Cited By ~ 2

Author(s):

S Vickers

Keyword(s):

Multidrug Resistance ◽

Cho Cells ◽

Glycoprotein Gene ◽

P Glycoprotein ◽

Gene Transcripts

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The three mouse multidrug resistance (mdr) genes are expressed in a tissue-specific manner in normal mouse tissues.

Molecular and Cellular Biology ◽

10.1128/mcb.9.3.1346 ◽

1989 ◽

Vol 9 (3) ◽

pp. 1346-1350 ◽

Cited By ~ 347

Author(s):

J M Croop ◽

M Raymond ◽

D Haber ◽

A Devault ◽

R J Arceci ◽

...

Keyword(s):

Multidrug Resistance ◽

Multigene Family ◽

Physiological Function ◽

Rna Transcripts ◽

P Glycoprotein ◽

Mouse Tissues ◽

Gene Transcripts ◽

Normal Physiological Function ◽

Rna Transcript ◽

Mdr Genes

The gene responsible for multidrug resistance (mdr), which encodes the P-glycoprotein, is a member of a multigene family. We have identified distinct mdr gene transcripts encoded by three separate mdr genes in the mouse. Expression levels of each mdr gene are dramatically different in various mouse tissues. Specific mdr RNA transcripts of approximately 4.5, 5, and 6 kilobases have been detected. Each of the mdr genes has a specific RNA transcript pattern. These results should be considered in relation to understanding the normal physiological function of the mdr multigene family.

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The three mouse multidrug resistance (mdr) genes are expressed in a tissue-specific manner in normal mouse tissues

Molecular and Cellular Biology ◽

10.1128/mcb.9.3.1346-1350.1989 ◽

1989 ◽

Vol 9 (3) ◽

pp. 1346-1350

Author(s):

J M Croop ◽

M Raymond ◽

D Haber ◽

A Devault ◽

R J Arceci ◽

...

Keyword(s):

Multidrug Resistance ◽

Multigene Family ◽

Physiological Function ◽

Rna Transcripts ◽

P Glycoprotein ◽

Mouse Tissues ◽

Gene Transcripts ◽

Normal Physiological Function ◽

Rna Transcript ◽

Mdr Genes

The gene responsible for multidrug resistance (mdr), which encodes the P-glycoprotein, is a member of a multigene family. We have identified distinct mdr gene transcripts encoded by three separate mdr genes in the mouse. Expression levels of each mdr gene are dramatically different in various mouse tissues. Specific mdr RNA transcripts of approximately 4.5, 5, and 6 kilobases have been detected. Each of the mdr genes has a specific RNA transcript pattern. These results should be considered in relation to understanding the normal physiological function of the mdr multigene family.

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Structure and expression of the human MDR (P-glycoprotein) gene family.

Molecular and Cellular Biology ◽

10.1128/mcb.9.9.3808 ◽

1989 ◽

Vol 9 (9) ◽

pp. 3808-3820 ◽

Cited By ~ 189

Author(s):

J E Chin ◽

R Soffir ◽

K E Noonan ◽

K Choi ◽

I B Roninson

Keyword(s):

Gene Family ◽

Cell Lines ◽

Efflux Pump ◽

Expression Patterns ◽

Multidrug Resistant ◽

Resistant Cell ◽

Mdr1 Gene ◽

Glycoprotein Gene ◽

P Glycoprotein ◽

Mdr Genes

The human MDR (P-glycoprotein) gene family is known to include two members, MDR1 and MDR2. The product of the MDR1 gene, which is responsible for resistance to different cytotoxic drugs (multidrug resistance), appears to serve as an energy-dependent efflux pump for various lipophilic compounds. The function of the MDR2 gene remains unknown. We have examined the structure of the human MDR gene family by Southern hybridization of DNA from different multidrug-resistant cell lines with subfragments of MDR1 cDNA and by cloning and sequencing of genomic fragments. We have found no evidence for any other cross-hybridizing MDR genes. The sequence of two exons of the MDR2 gene was determined from genomic clones. Hybridization with single-exon probes showed that the human MDR1 gene is closely related to two genes in mouse and hamster DNA, whereas MDR2 corresponds to one rodent gene. The human MDR locus was mapped by field-inversion gel electrophoresis, and both MDR genes were found to be linked within 330 kilobases. The expression patterns of the human MDR genes were examined by enzymatic amplification of cDNA. In multidrug-resistant cell lines, increased expression of MDR1 mRNA was paralleled by a smaller increase in the levels of MDR2 mRNA. In normal human tissues, MDR2 was coexpressed with MDR1 in the liver, kidney, adrenal gland, and spleen. MDR1 expression was also detected in colon, lung, stomach, esophagus, muscle, breast, and bladder.

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Evolutionary Pattern and Regulation Analysis to Support Why Diversity Functions Existed within PPAR Gene Family Members

BioMed Research International ◽

10.1155/2015/613910 ◽

2015 ◽

Vol 2015 ◽

pp. 1-11 ◽

Cited By ~ 6

Author(s):

Tianyu Zhou ◽

Xiping Yan ◽

Guosong Wang ◽

Hehe Liu ◽

Xiang Gan ◽

...

Keyword(s):

Gene Duplication ◽

Gene Family ◽

Hormone Receptors ◽

Expression Patterns ◽

Family Members ◽

Duplication Event ◽

Promoter Regions ◽

Evolutionary Pattern ◽

Duplication Events ◽

Differential Transcription

Peroxisome proliferators-activated receptor (PPAR) gene family members exhibit distinct patterns of distribution in tissues and differ in functions. The purpose of this study is to investigate the evolutionary impacts on diversity functions of PPAR members and the regulatory differences on gene expression patterns. 63 homology sequences of PPAR genes from 31 species were collected and analyzed. The results showed that three isolated types of PPAR gene family may emerge from twice times of gene duplication events. The conserved domains of HOLI (ligand binding domain of hormone receptors) domain and ZnF_C4 (C4 zinc finger in nuclear in hormone receptors) are essential for keeping basic roles of PPAR gene family, and the variant domains of LCRs may be responsible for their divergence in functions. The positive selection sites in HOLI domain are benefit for PPARs to evolve towards diversity functions. The evolutionary variants in the promoter regions and 3′ UTR regions of PPARs result into differential transcription factors and miRNAs involved in regulating PPAR members, which may eventually affect their expressions and tissues distributions. These results indicate that gene duplication event, selection pressure on HOLI domain, and the variants on promoter and 3′ UTR are essential for PPARs evolution and diversity functions acquired.

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Physical mapping, amplification, and overexpression of the mouse mdr gene family in multidrug-resistant cells.

Molecular and Cellular Biology ◽

10.1128/mcb.10.4.1642 ◽

1990 ◽

Vol 10 (4) ◽

pp. 1642-1651 ◽

Cited By ~ 95

Author(s):

M Raymond ◽

E Rose ◽

D E Housman ◽

P Gros

Keyword(s):

Molecular Weight ◽

Multidrug Resistance ◽

Gene Family ◽

Cell Lines ◽

Gene Amplification ◽

Genomic Dna ◽

Multidrug Resistant ◽

Pulse Field ◽

P Glycoprotein ◽

Mdr Genes

The mouse mdr gene family consists of three distinct genes (mdr1, mdr2, and mdr3), for which we have isolated full-length cDNA clones. cDNA subfragments corresponding to discrete regions showing little sequence conservation among the three mdr genes were used as gene-specific DNA probes in hybridization experiments. Long-range mapping by pulse-field gel electrophoresis indicated that the three mdr genes are closely linked on a genomic DNA segment of approximately 625 kilobases. The gene order and direction of transcription of the three genes were determined and indicate the arrangement (5') mdr3 (3')-(5') mdr1 (3')-(3') mdr2 (5'). Southern blotting analyses of genomic DNA from a panel of independently derived multidrug-resistant cell lines identified mdr gene amplification in 10 of 12 cell lines studied. In individual cell lines showing gene amplification, the copy number of each of the three mdr genes was identical, suggesting that the three mdr genes became amplified as part of a single amplicon in these cells. Although increased expression of all three mdr genes was detected in 2 of 12 cell lines tested, multidrug resistance was associated in 10 of 12 lines with the independent overexpression of either mdr1 (7 of 12) or mdr3 (3 of 12) but not mdr2. mdr1 overexpression was consistently associated with gene amplification, while increased mdr3 expression was detected in certain cell lines that did not show gene amplification. Increased levels of mdr1 mRNA were linked to the overexpression of a P glycoprotein of apparent molecular weight 180,000 to 200,000, whereas increased mdr3 expression resulted in increased expression of a P glycoprotein of molecular weight 160,000 to 180,000. Our results suggest that at least two members of the mouse mdr gene family, mdr1 and mdr3, can independently confer multidrug resistance in the cell lines examined.

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