Amplification and expression of genes associated with multidrug resistance in mammalian cells

Science ◽  
1986 ◽  
Vol 232 (4751) ◽  
pp. 751-755 ◽  
Author(s):  
K. Scotto ◽  
J. Biedler ◽  
P. Melera
Keyword(s):  
Multidrug Resistance ◽  
Mammalian Cells ◽  
Expression Of Genes

Oxygen sensing and molecular adaptation to hypoxia

1996 ◽  
Vol 76 (3) ◽  
pp. 839-885 ◽  
Author(s):  
H. F. Bunn ◽  
R. O. Poyton
Keyword(s):  
Transcription Factors ◽  
Mammalian Cells ◽  
Critical Role ◽  
Hypoxia Inducible Factor ◽  
Signal Transduction Pathway ◽  
Adaptation To Hypoxia ◽  
Adaptive Responses ◽  
Expression Of Genes ◽  
Activation Of Transcription ◽  
Activation Of Oxygen

This review focuses on the molecular stratagems utilized by bacteria, yeast, and mammals in their adaptation to hypoxia. Among this broad range of organisms, changes in oxygen tension appear to be sensed by heme proteins, with subsequent transfer of electrons along a signal transduction pathway which may depend on reactive oxygen species. These heme-based sensors are generally two-domain proteins. Some are hemokinases, while others are flavohemoproteins [flavohemoglobins and NAD(P)H oxidases]. Hypoxia-dependent kinase activation of transcription factors in nitrogen-fixing bacteria bears a striking analogy to the phosphorylation of hypoxia inducible factor-1 (HIF-1) in mammalian cells. Moreover, redox chemistry appears to play a critical role both in the trans-activation of oxygen-responsive genes in unicellular organisms as well as in the activation of HIF-1. In yeast and bacteria, regulatory operons coordinate expression of genes responsible for adaptive responses to hypoxia and hyperoxia. Similarly, in mammals, combinatorial interactions of HIF-1 with other identified transcription factors are required for the hypoxic induction of physiologically important genes.

scholarly journals Reversal of Mefloquine and Quinine Resistance in Plasmodium falciparum with NP30

2003 ◽  
Vol 47 (8) ◽  
pp. 2393-2396 ◽  
Author(s):  
Michelle Ciach ◽  
Kathleen Zong ◽  
Kevin C. Kain ◽  
Ian Crandall
Keyword(s):  
Plasmodium Falciparum ◽  
Multidrug Resistance ◽  
Genetic Analysis ◽  
Resistance Genes ◽  
Mammalian Cells ◽  
Point Mutations ◽  
In Vitro Assays ◽  
Drug Efflux ◽  
P Glycoprotein

ABSTRACT Quinoline resistance in malaria is frequently compared with P-glycoprotein-mediated multidrug resistance (mdr) in mammalian cells. We have previously reported that nonylphenolethoxylates, such as NP30, are potential Plasmodium falciparum P-glycoprotein substrates and drug efflux inhibitors. We used in vitro assays to compare the ability of verapamil and NP30 to sensitize two parasite isolates to four quinolines: chloroquine (CQ), mefloquine (MF), quinine (QN), and quinidine (QD). NP30 was able to sensitize (reversal, >80%) P. falciparum to MF, QN, QD, and, to a lesser extent, CQ. The presence of 2 μM verapamil had no effect on mefloquine resistance; however, the presence of verapamil modulated the activities of QN and QD in a manner parallel to that observed for CQ. Genetic analysis of putative quinoline resistance genes did not suggest an association between known point mutations in pfcrt and pfmdr1 and NP30 sensitization activity. We conclude that the sensitization action of NP30 is distinct both phenotypically and genotypically from that of verapamil.

scholarly journals Expression of genes and proteins of multidrug resistance in gastric cancer cells treated with resveratrol

2018 ◽  
Author(s):  
Katarzyna Mieszala ◽  
Malgorzata Rudewicz ◽  
Agnieszka Gomulkiewicz ◽  
Katarzyna Ratajczak‑Wielgomas ◽  
Jedrzej Grzegrzolka ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Multidrug Resistance ◽  
Cancer Cells ◽  
Gastric Cancer Cells ◽  
Expression Of Genes

scholarly journals Functional expression of P-glycoprotein in Saccharomyces cerevisiae confers cellular resistance to the immunosuppressive and antifungal agent FK520

1994 ◽  
Vol 14 (1) ◽  
pp. 277-286
Author(s):  
M Raymond ◽  
S Ruetz ◽  
D Y Thomas ◽  
P Gros
Keyword(s):  
Multidrug Resistance ◽  
Mammalian Cells ◽  
Drug Transport ◽  
Function Analysis ◽  
Expression System ◽  
Functional Expression ◽  
Yeast Cells ◽  
Mutant Form ◽  
Cellular Resistance ◽  
P Glycoprotein

We have recently reported that expression in yeast cells of P-glycoprotein (P-gp) encoded by the mouse multidrug resistance mdr3 gene (Mdr3) can complement a null ste6 mutation (M. Raymond, P. Gros, M. Whiteway, and D. Y. Thomas, Science 256:232-234, 1992). Here we show that Mdr3 behaves as a fully functional drug transporter in this heterologous expression system. Photolabelling experiments indicate that Mdr3 synthesized in yeast cells binds the drug analog [125I]iodoaryl azidoprazosin, this binding being competed for by vinblastine and tetraphenylphosphonium bromide, two known multidrug resistance drugs. Spheroplasts expressing wild-type Mdr3 (Ser-939) exhibit an ATP-dependent and verapamil-sensitive decreased accumulation of [3H]vinblastine as compared with spheroplasts expressing a mutant form of Mdr3 with impaired transport activity (Phe-939). Expression of Mdr3 in yeast cells can confer resistance to growth inhibition by the antifungal and immunosuppressive agent FK520, suggesting that this compound is a substrate for P-gp in yeast cells. Replacement of Ser-939 in Mdr3 by a series of amino acid substitutions is shown to modulate both the level of cellular resistance to FK520 and the mating efficiency of yeast mdr3 transformants. The effects of these mutations on the function of Mdr3 in yeast cells are similar to those observed in mammalian cells with respect to drug resistance and transport, indicating that transport of a-factor and FK520 in yeast cells is mechanistically similar to drug transport in mammalian cells. The ability of P-gp to confer cellular resistance to FK520 in yeast cells establishes a dominant phenotype that can be assayed for the positive selection of intragenic revertants of P-gp inactive mutants, an important tool for the structure-function analysis of mammalian P-gp in yeast cells.

Expression of genes for thioredoxin 1 and thioredoxin 2 in multidrug resistance ovarian carcinoma cells SKVLB

2007 ◽  
Vol 144 (3) ◽  
pp. 301-303 ◽  
Author(s):  
E. V. Kalinina ◽  
N. N. Chernov ◽  
A. N. Saprin ◽  
Ya. N. Kotova ◽  
Yu. A. Gavrilova ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Ovarian Carcinoma ◽  
Carcinoma Cells ◽  
Ovarian Carcinoma Cells ◽  
Expression Of Genes ◽  
Thioredoxin 1 ◽  
Thioredoxin 2

scholarly journals Tor and Cyclic AMP-Protein Kinase A: Two Parallel Pathways Regulating Expression of Genes Required for Cell Growth

2005 ◽  
Vol 4 (1) ◽  
pp. 63-71 ◽  
Author(s):  
Sara A. Zurita-Martinez ◽  
Maria E. Cardenas
Keyword(s):  
Gene Expression ◽  
Protein Kinase ◽  
Cell Growth ◽  
Cyclic Amp ◽  
Protein Kinase A ◽  
Mammalian Cells ◽  
Regulatory Networks ◽  
Expression Of Genes ◽  
Transcriptional Pattern ◽  
Kinase A

ABSTRACT In the budding yeast Saccharomyces cerevisiae, the Tor and cyclic AMP-protein kinase A (cAMP-PKA) signaling cascades respond to nutrients and regulate coordinately the expression of genes required for cell growth, including ribosomal protein (RP) and stress-responsive (STRE) genes. The inhibition of Tor signaling by rapamycin results in repression of the RP genes and induction of the STRE genes. Mutations that hyperactivate PKA signaling confer resistance to rapamycin and suppress the repression of RP genes imposed by rapamycin. By contrast, partial inactivation of PKA confers rapamycin hypersensitivity but only modestly affects RP gene expression. Complete inactivation of PKA impairs RP gene expression and concomitantly enhances STRE gene expression; remarkably, this altered transcriptional pattern is still sensitive to rapamycin and thus subject to Tor control. These findings illustrate how the Tor and cAMP-PKA signaling pathways respond to nutrient signals to govern gene expression required for cell growth via two parallel routes, and they have broad implication for our understanding of analogous regulatory networks in normal and neoplastic mammalian cells.

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