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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
MeSH Review

Genes, MDR

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Disease relevance of Genes, MDR


High impact information on Genes, MDR

  • The existence of an mdr gene in P. falciparum and its amplification in some chloroquine-resistant lines greatly adds to the circumstantial evidence that pfmdr mediates chloroquine resistance in these lines [6].
  • A homologue (pfmdr1) of the mammalian multidrug resistance gene has been implicated in CQR because it is amplified in some CQR isolates of P. falciparum as is an mdr gene in MDR tumour cells [7].
  • Tissue-specific expression of MDR1 and other members of the MDR gene family has been observed in normal cells, suggesting a role for P-glycoproteins in secretion [8].
  • Functional complementation of yeast ste6 by a mammalian multidrug resistance mdr gene [9].
  • Levels of messenger RNA for the mdr gene, which encodes P-glycoprotein, were elevated in both preneoplastic and neoplastic lesions [10].

Chemical compound and disease context of Genes, MDR


Biological context of Genes, MDR


Anatomical context of Genes, MDR

  • We now demonstrate that topical colchicine treatment can be used to select, in vivo, KC progenitor cells transduced with the multidrug resistance gene (MDR1) [18].
  • Progenitor assays in methylcellulose at this time showed that 18% to 70% of BFU-E and 30% to 60% of CFU-GM contain the transferred MDR gene by polymerase chain reaction analysis [19].
  • To evaluate the possible role of this protease in the transformed phenotype, we transfected cloned genes for mouse or human MEP into mouse NIH 3T3 cells with an expression vector for the dominant, selectable human multidrug resistance (MDR1) gene [20].
  • Our studies were conducted with multidrug-resistant KB cells, which harbor extrachromosomal copies of the multidrug resistance gene (MDR1) almost exclusively on circular DNA molecules of approximately 750 and 1500 kb pairs [21].
  • In rat pancreatic zymogen granules (ZG), an ATP-sensitive K(+) conductance and a Cl(-) conductance have been characterized that are inversely regulated by an approximately 65-kDa multidrug resistance P-glycoprotein (mdr1) gene product [22].

Associations of Genes, MDR with chemical compounds


Gene context of Genes, MDR

  • Multidrug resistance (MDR) genes, which are ATP-binding cassette family genes, encode the cell surface glycoprotein, P-glycoprotein, which functions as an energy-dependent drug efflux pump [27].
  • Considerable evidence has accumulated indicating that overexpression of P-glycoproteins encoded by the multidrug-resistance (mdr) genes is responsible for the development of collateral resistance to a number of structurally and functionally dissimilar cytotoxic compounds in animal cells [28].
  • We previously reported that only one of the three mouse multidrug-resistance (mdr) genes, mdr3, is activated in hepatocellular carcinomas (HCCs) [29].
  • Although the physiological role of MRP is not yet understood, one Pgp gene (mdr1) plays an important role in the blood-tissue barrier and the other (mdr2/3) is involved in phospholipid transport in the liver [30].
  • In mammals, many xenobiotics induce the expression of cytochrome P4503A (CYP3A) and the multiple drug resistance 1 (MDR1) genes via the PXR pathway [31].

Analytical, diagnostic and therapeutic context of Genes, MDR


  1. Chemosensitivity patterns and expression of human multidrug resistance-associated MDR1 gene by human gastric and colorectal carcinoma cell lines. Park, J.G., Kramer, B.S., Lai, S.L., Goldstein, L.J., Gazdar, A.F. J. Natl. Cancer Inst. (1990) [Pubmed]
  2. The multidrug resistance and cystic fibrosis genes have complementary patterns of epithelial expression. Trezise, A.E., Romano, P.R., Gill, D.R., Hyde, S.C., Sepúlveda, F.V., Buchwald, M., Higgins, C.F. EMBO J. (1992) [Pubmed]
  3. A bacterial analog of the mdr gene of mammalian tumor cells is present in Streptomyces peucetius, the producer of daunorubicin and doxorubicin. Guilfoile, P.G., Hutchinson, C.R. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  4. Multidrug resistance (mdr1) gene expression in adult acute leukemias: correlations with treatment outcome and in vitro drug sensitivity. Marie, J.P., Zittoun, R., Sikic, B.I. Blood (1991) [Pubmed]
  5. Inhibition of P-glycoprotein and recovery of drug sensitivity of human acute leukemic blast cells by multidrug resistance gene (mdr1) antisense oligonucleotides. Motomura, S., Motoji, T., Takanashi, M., Wang, Y.H., Shiozaki, H., Sugawara, I., Aikawa, E., Tomida, A., Tsuruo, T., Kanda, N., Mizoguchi, H. Blood (1998) [Pubmed]
  6. Amplification of the multidrug resistance gene in some chloroquine-resistant isolates of P. falciparum. Foote, S.J., Thompson, J.K., Cowman, A.F., Kemp, D.J. Cell (1989) [Pubmed]
  7. Several alleles of the multidrug-resistance gene are closely linked to chloroquine resistance in Plasmodium falciparum. Foote, S.J., Kyle, D.E., Martin, R.K., Oduola, A.M., Forsyth, K., Kemp, D.J., Cowman, A.F. Nature (1990) [Pubmed]
  8. The yeast STE6 gene encodes a homologue of the mammalian multidrug resistance P-glycoprotein. McGrath, J.P., Varshavsky, A. Nature (1989) [Pubmed]
  9. Functional complementation of yeast ste6 by a mammalian multidrug resistance mdr gene. Raymond, M., Gros, P., Whiteway, M., Thomas, D.Y. Science (1992) [Pubmed]
  10. Expression of the multidrug-resistant gene in hepatocarcinogenesis and regenerating rat liver. Thorgeirsson, S.S., Huber, B.E., Sorrell, S., Fojo, A., Pastan, I., Gottesman, M.M. Science (1987) [Pubmed]
  11. Biological activity of a fruit vegetable, "Anastasia green", a species of sweet pepper. Motohashi, N., Kurihara, T., Wakabayashi, H., Yaji, M., Mucsi, I., Molnár, J., Maruyama, S., Sakagami, H., Nakashima, H., Tani, S., Shirataki, Y., Kawase, M. In Vivo (2001) [Pubmed]
  12. Concerning antisense inhibition of the multiple drug resistance gene. Jaroszewski, J.W., Kaplan, O., Syi, J.L., Sehested, M., Faustino, P.J., Cohen, J.S. Cancer Commun. (1990) [Pubmed]
  13. Modulation of activity of the promoter of the human MDR1 gene by Ras and p53. Chin, K.V., Ueda, K., Pastan, I., Gottesman, M.M. Science (1992) [Pubmed]
  14. Isolation of human mdr DNA sequences amplified in multidrug-resistant KB carcinoma cells. Roninson, I.B., Chin, J.E., Choi, K.G., Gros, P., Housman, D.E., Fojo, A., Shen, D.W., Gottesman, M.M., Pastan, I. Proc. Natl. Acad. Sci. U.S.A. (1986) [Pubmed]
  15. Mammalian multidrug-resistance gene: correlation of exon organization with structural domains and duplication of an ancestral gene. Raymond, M., Gros, P. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  16. Expression of retroviral vectors containing the human multidrug resistance 1 cDNA in hematopoietic cells of transplanted mice. Sorrentino, B.P., McDonagh, K.T., Woods, D., Orlic, D. Blood (1995) [Pubmed]
  17. Hypomethylation status of CpG sites at the promoter region and overexpression of the human MDR1 gene in acute myeloid leukemias. Nakayama, M., Wada, M., Harada, T., Nagayama, J., Kusaba, H., Ohshima, K., Kozuru, M., Komatsu, H., Ueda, R., Kuwano, M. Blood (1998) [Pubmed]
  18. Topical colchicine selection of keratinocytes transduced with the multidrug resistance gene (MDR1) can sustain and enhance transgene expression in vivo. Pfutzner, W., Terunuma, A., Tock, C.L., Snead, E.K., Kolodka, T.M., Gottesman, M.M., Taichman, L., Vogel, J.C. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  19. Transfer and expression of the human multiple drug resistance gene in human CD34+ cells. Ward, M., Richardson, C., Pioli, P., Smith, L., Podda, S., Goff, S., Hesdorffer, C., Bank, A. Blood (1994) [Pubmed]
  20. Use of a cloned multidrug resistance gene for coamplification and overproduction of major excreted protein, a transformation-regulated secreted acid protease. Kane, S.E., Troen, B.R., Gal, S., Ueda, K., Pastan, I., Gottesman, M.M. Mol. Cell. Biol. (1988) [Pubmed]
  21. Fractionated ionizing radiation accelerates loss of amplified MDR1 genes harbored by extrachromosomal DNA in tumor cells. Sanchez, A.M., Barrett, J.T., Schoenlein, P.V. Cancer Res. (1998) [Pubmed]
  22. Photoaffinity labeling and purification of ZG-16p, a high-affinity dihydropyridine binding protein of rat pancreatic zymogen granule membranes that regulates a K(+)-selective conductance. Braun, M., Thévenod, F. Mol. Pharmacol. (2000) [Pubmed]
  23. Multidrug resistance-like genes of Arabidopsis required for auxin transport and auxin-mediated development. Noh, B., Murphy, A.S., Spalding, E.P. Plant Cell (2001) [Pubmed]
  24. Characterization of the multidrug resistance protein expressed in cell clones stably transfected with the mouse mdr1 cDNA. Schurr, E., Raymond, M., Bell, J.C., Gros, P. Cancer Res. (1989) [Pubmed]
  25. Reversal of multidrug resistance by RU 486. Gruol, D.J., Zee, M.C., Trotter, J., Bourgeois, S. Cancer Res. (1994) [Pubmed]
  26. Expression of multidrug resistance genes in rat liver during regeneration and after carbon tetrachloride intoxication. Nakatsukasa, H., Silverman, J.A., Gant, T.W., Evarts, R.P., Thorgeirsson, S.S. Hepatology (1993) [Pubmed]
  27. Functional expression of yeast artificial chromosome-human multidrug resistance genes in mouse cells. Kusaba, H., Kohno, K., Asakuno, K., Kuwano, M., Okumura, K., Green, E.D., Schlessinger, D., Wada, M. Genome Res. (1995) [Pubmed]
  28. Modulation of multidrug resistance gene expression by dexamethasone in cultured hepatoma cells. Zhao, J.Y., Ikeguchi, M., Eckersberg, T., Kuo, M.T. Endocrinology (1993) [Pubmed]
  29. Coordinate activation of multidrug-resistance (P-glycoprotein) genes mdr2 and mdr3 during mouse liver regeneration. Teeter, L.D., Chan, J.Y., Kuo, M.T. Mol. Carcinog. (1991) [Pubmed]
  30. Multidrug resistance: molecular mechanisms and clinical relevance. Ling, V. Cancer Chemother. Pharmacol. (1997) [Pubmed]
  31. Expression of PXR, CYP3A and MDR1 genes in liver of zebrafish. Bresolin, T., de Freitas Rebelo, M., Celso Dias Bainy, A. Comp. Biochem. Physiol. C Toxicol. Pharmacol. (2005) [Pubmed]
  32. The common marmoset as a target preclinical primate model for cytokine and gene therapy studies. Hibino, H., Tani, K., Ikebuchi, K., Wu, M.S., Sugiyama, H., Nakazaki, Y., Tanabe, T., Takahashi, S., Tojo, A., Suzuki, S., Tanioka, Y., Sugimoto, Y., Nakahata, T., Asano, S. Blood (1999) [Pubmed]
  33. Ascorbic acid increases drug accumulation and reverses vincristine resistance of human non-small-cell lung-cancer cells. Chiang, C.D., Song, E.J., Yang, V.C., Chao, C.C. Biochem. J. (1994) [Pubmed]
  34. Methylation analysis of the human multidrug resistance 1 gene in normal and leukemic hematopoietic cells. Fryxell, K.B., McGee, S.B., Simoneaux, D.K., Willman, C.L., Cornwell, M.M. Leukemia (1999) [Pubmed]
  35. Expression of a multidrug resistance gene in esophageal adenocarcinoma. Correlation with response to chemotherapy and comparison with gastric adenocarcinoma. Robey-Cafferty, S.S., Rutledge, M.L., Bruner, J.M. Am. J. Clin. Pathol. (1990) [Pubmed]
  36. P-glycoprotein expression in Ehrlich ascites tumour cells after in vitro and in vivo selection with daunorubicin. Nielsen, D., Eriksen, J., Maare, C., Jakobsen, A.H., Skovsgaard, T. Br. J. Cancer (1998) [Pubmed]
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