Expression of the mdr (P-glycoprotein) Gene in Chinese Hamster Digestive Tracts1

Mukhopadhyay, Tapas; Batsakis, John G.; Kuo, Marcus Tien

doi:10.1093/jnci/80.4.269

Cited by 38 publications

(6 citation statements)

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“…MDR gene expression in the intestinal epithelium has been reported by numerous investigators in human (Fojo et al, 1987;Thiebaut et al, 1987), mouse (Croop et al, 1989;Buschman et al, 1992), hamster (Mukhopadhyay et al, 1988;Bradley et al, 1990) and rat (Trezise and Buchwald, 1991). These studies have all identified the class I gene (MDR1, mdr1a and pgp1 respectively) as the only isoform in the intestinal epithelium.…”

Section: Discussionmentioning

confidence: 90%

Regulation and expression of multidrug resistance (MDR) transcripts in the intestinal epithelium

Hurren

Zastawny

et al. 1999

Br J Cancer

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Summary A paucity of information exists on the regulation of gene expression in the undifferentiated intestine. The intestinal epithelium is one of the few normal tissues expressing the multidrug resistance (MDR) genes that confer the multidrug resistant phenotype to a variety of tumours. Expression of mdr1a has been observed in the primitive rat intestinal epithelial cell line, IEC-18. It is hypothesized that characterization of MDR gene expression in IEC-18 cells will provide insight into gene regulation in undifferentiated intestinal cells. A series of hamster mdr1a promoter deletion constructs was studied in IEC-18 and a region with 12-13-fold enhancer activity was identified. This region was shown to function in an orientation-and promoter context-independent manner, specifically in IEC-18 cells. Unexpectedly, Northern probing revealed a greater expression of mdr1b than mdr1a in IEC-18 cells. A quantitative reverse transcription polymerase chain reaction assay was used to compare the relative expression of MDR genes in IEC cells, fetal intestine, and in the undifferentiated and differentiated components of adult intestinal epithelium. MDR transcript levels in IEC cells were found to resemble those of fetal intestine and small intestinal crypts, where a conversion from mixed mdr1a/mdr1b to predominantly mdr1a expression occurs as cells mature. This work describes two contributions to the field of gene regulation in the undifferentiated intestine -first, the initial characterization of a putative mdr1a enhancer region with specificity for primitive intestinal cells and secondly, the first report of mdr1b detection in the intestine and its expression in primitive cell types.

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Section: Discussionmentioning

confidence: 90%

Regulation and expression of multidrug resistance (MDR) transcripts in the intestinal epithelium

Hurren

Zastawny

et al. 1999

Br J Cancer

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“…MDR1-type P-glycoprotein has been found in the apical membrane of the intestinal epithelial cells (Mukhopadhyay et al 1988), in the biliary canalicular membrane of hepatocytes, and in the lumenal membrane of proximal tubular epithelial cells in the kidney (Thiebaut et al 1987(Thiebaut et al , 1989. High levels of MDR1 P-glycoprotein have been found in the lumenal membrane of the endothelial cells that line small blood capillaries and form the blood-brain and blood-testis barrier (Thiebaut et al 1989;Cordon-Cardo et al 1989Tsuji et al 1992).…”

Section: Mice With a Genetic Disruption (Knockout) Of The Multiple Drmentioning

confidence: 99%

Penetration of Amitriptyline, but Not of Fluoxetine, into Brain is Enhanced in Mice with Blood-Brain Barrier Deficiency Due to Mdr1a P-Glycoprotein Gene Disruption

Uhr

Steckler

Yassouridis

et al. 2000

Neuropsychopharmacology

215

152

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Mice with a genetic disruption (knockout) of the multiple drug resistance (Mdr1a) gene were used to examine the effect of the absence of the drug-transporting P-glycoproteinat the blood-brain barrier on the uptake of amitriptyline (AMI) and fluoxetine (FLU) P-glycoprotein is encoded by the MDR1 gene in humans and the mdr1a (also called mdr3) and mdr1b (also called mdr1) gene in mice (Devault and Gros 1990). Although mdr1a and mdr1b are not always expressed in the same organs, the overall distribution of these genes in mice tissue coincides roughly with that of the single MDR1 gene in humans, suggesting that mdr1a and From the

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“…Consistent with this idea, it has been suggested that P-glycoproteins play an important role in the excretory systems of normal animals. In situ hybridization (36) and immunocytochemical analyses (18,46) have demonstrated high levels of mdr transcripts or P-glycoprotein on the lumenal surface of several epithelial cell types, including hepatocytes, intestinal mucosal epithelial cells, and kidney proximal tubule cells.…”

mentioning

confidence: 99%

Overexpression of the multidrug resistance gene mdr3 in spontaneous and chemically induced mouse hepatocellular carcinomas.

Teeter¹,

Becker²,

Chisari³

et al. 1990

Mol. Cell. Biol.

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Overexpression of a family of plasma membrane glycoproteins, known as P-glycoproteins, is commonly associated with multidrug resistance in animal cells. In rodents, three multidrug resistance (mdr or pgp) genes have been identified, but only two can confer the multidrug resistance phenotype upon transfection into animal cells. Using the RNase protection method, we demonstrated that the levels of three mdr gene transcripts differ among mouse tissues, confirming a previous report that the expression of these genes is tissue specific (J. M. Croop, M. Raymond, D. Huber, A. DeVault, R. J. Arceci, P. Gros, and D. E Housman, Mol. Cell. Biol. 9:1346Biol. 9: -1350Biol. 9: , 1989. The levels of mdr transcripts were determined for mouse liver tumors spontaneously arising in both C3H/HeN and transgenic animals containing the hepatitis B virus envelope gene and for tumors induced by two different carcinogenic regimens in C57BL/6N and B6C3-F1 mice. The mdr3 gene was overexpressed in all 22 tumors tested. Our results demonstrate that overexpression of the mdr3 gene in mouse liver tumors does not require exposure of the animals to carcinogenic agents and suggest that its overexpression is associated with a general pathway of hepatic tumor development. The overexpression of the mdr3 gene, which is the homolog of human mdrl gene, in hepatocellular carcinomas may be responsible for the poor response of these tumors to cancer chemotherapeutic agents.The involvement of multidrug resistance (mdr, also known as P-glycoprotein, pgp) genes in the development of resistance to a variety of hydrophobic antineoplastic compounds in animal cells and in human tumors has been established in recent years (for reviews, see references 11, 14, 22, and 30). Three mdr genes have been reported in rodents, while only two have been identified in humans. In the mouse, the full-length cDNAs for mdrl (25) Predicted structural features of P-glycoprotein (5, 25) derived from the amino acid sequences deduced from cloned cDNAs, as well as photoaffinity cross-linking studies (9, 41), have led to a proposal suggesting that these proteins function in MDR cells by forming pores in the membrane through which they actively expel intracellular antineoplastic compounds. Consistent with this idea, it has been suggested that P-glycoproteins play an important role in the excretory systems of normal animals. In situ hybridization (36) and immunocytochemical analyses (18,46)

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Expression of the mdr (P-glycoprotein) Gene in Chinese Hamster Digestive Tracts1

Cited by 38 publications

References 0 publications

Regulation and expression of multidrug resistance (MDR) transcripts in the intestinal epithelium

Regulation and expression of multidrug resistance (MDR) transcripts in the intestinal epithelium

Penetration of Amitriptyline, but Not of Fluoxetine, into Brain is Enhanced in Mice with Blood-Brain Barrier Deficiency Due to Mdr1a P-Glycoprotein Gene Disruption

Overexpression of the multidrug resistance gene mdr3 in spontaneous and chemically induced mouse hepatocellular carcinomas.

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