ABC Proteins and Oncology: Expression, Detection, and Implication of ABC Proteins in Solid Tumors

Bernaudin, J.-F.; Fajac, Anne; Fleury‐Feith, Jocelyne; Kerrou, Khaldoun; Lacave, Roger

doi:10.1002/9780470495131.ch5

Cited by 5 publications

(7 citation statements)

References 117 publications

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“…In phase 0, ABCBs would transport toxicants that do not have enzymatic modifications out of the cell. In phase III, ABCC and ABCG transporter subfamilies would transport toxicants that were modified by detoxifying enzymes during phases I and II (e.g., CYP450, GSTs, or UDP-glycosyltransferases) out of the cell 2 3 . Our data appeared to support the role of ABCB transporters early after insecticide treatment.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, ABCG4 was also overexpressed at early time points after treatment, with the highest value observed at 6 h. This observation indicated that this ABC subfamily could play a role during the initial phase of the detoxification process. Moreover, while studies have shown that the detoxification process can be subdivided into different phases in which different enzymatic complexes act, the time after insecticide treatment at which each single phase starts is unknown 2 3 . Future genome-wide expression studies, carried out at different time points after insecticide treatment, could help to elucidate the interplay among the protein complexes involved in the detoxification process, including phase I and phase II enzymes and ABC transporters.…”

Section: Discussionmentioning

confidence: 99%

“…The effects of these molecules can be mitigated by enzymatic complexes that function to detoxify cells, called drug metabolizing enzymes (DMEs) 1 . The defensive function of DMEs can be subdivided into different phases, which involve a variety of protein complexes 1 2 3 . In phase I, oxidation, reduction, and chemical cleavage of toxic compounds occur through the actions of cytochrome P450 carboxylesterases.…”

mentioning

confidence: 99%

“…In phase 0, ABC transporters belonging to subfamilies ABCB (P-gps) and presumably ABCG, extrude toxicants out of the cells before enzymatic modifications of the compounds, therefore preventing the accumulation of these harmful toxicants inside the cells. In phase III, ABC transporters belonging to subfamilies ABCC (MRPs) and ABCG 2 extrude toxic molecules modified by phase II enzymes from the cells 2 3 . This DME-dependent defence mechanism is conserved among animals 1 .…”

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confidence: 99%

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Temporal dynamics of the ABC transporter response to insecticide treatment: insights from the malaria vector Anopheles stephensi

Epis

Porretta

Mastrantonio

et al. 2014

Sci Rep

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In insects, ABC transporters have been shown to contribute to defence/resistance to insecticides by reducing toxic concentrations in cells/tissues. Despite the extensive studies about this detoxifying mechanism, the temporal patterns of ABC transporter activation have been poorly investigated. Using the malaria vector Anopheles stephensi as a study system, we investigated the expression profile of ABC genes belonging to different subfamilies in permethrin-treated larvae at different time points (30 min to 48 h). Our results showed that the expression of ABCB and ABCG subfamily genes was upregulated at 1 h after treatment, with the highest expression observed at 6 h. Therefore, future investigations on the temporal dynamics of ABC gene expression will allow a better implementation of insecticide treatment regimens, including the use of specific inhibitors of ABC efflux pumps.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Temporal dynamics of the ABC transporter response to insecticide treatment: insights from the malaria vector Anopheles stephensi

Epis

Porretta

Mastrantonio

et al. 2014

Sci Rep

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“…Besides their elevated proliferative and invasive capacity, these cells also demonstrate high resistance to anticancer treatments, in particular, to chemotherapy (chemoresistance). One of the mechanisms behind chemoresistance is the overexpression of plasma membrane pumps (ABC transporters) which expel chemotherapeutics from the cell interior [3]. The overall functional characterization of MDR in TICs to date has been provided by a widely used flow cytometric side population assay.…”

Section: Introductionmentioning

confidence: 99%

Kinetics of MDR Transport in Tumor-Initiating Cells

2013

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Multidrug resistance (MDR) driven by ABC (ATP binding cassette) membrane transporters is one of the major causes of treatment failure in human malignancy. MDR capacity is thought to be unevenly distributed among tumor cells, with higher capacity residing in tumor-initiating cells (TIC) (though opposite finding are occasionally reported). Functional evidence for enhanced MDR of TICs was previously provided using a “side population” assay. This assay estimates MDR capacity by a single parameter - cell’s ability to retain fluorescent MDR substrate, so that cells with high MDR capacity (“side population”) demonstrate low substrate retention. In the present work MDR in TICs was investigated in greater detail using a kinetic approach, which monitors MDR efflux from single cells. Analysis of kinetic traces obtained allowed for the estimation of both the velocity (V max) and affinity (K M) of MDR transport in single cells. In this way it was shown that activation of MDR in TICs occurs in two ways: through the increase of V max in one fraction of cells, and through decrease of K M in another fraction. In addition, kinetic data showed that heterogeneity of MDR parameters in TICs significantly exceeds that of bulk cells. Potential consequences of these findings for chemotherapy are discussed.

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Single-Cell-Kinetics Approach to Compare Multidrug Resistance-Associated Membrane Transport in Subpopulations of Cells

Koshkin

Krylov

2011

Anal. Chem.

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Multidrug resistance (MDR) driven by active efflux of drugs from the cells is one of the major obstacles in chemotherapies. Understanding the nature of MDR and designing more efficient chemotherapies requires the comparison of the efflux rate between different subpopulations of cells. Here we propose a single-cell-kinetics approach for such a comparison. In essence, the entire cell population is loaded with a suitable fluorescent substrate for MDR-associated membrane transporters. The kinetics of substrate efflux from individual cells is followed by time-lapse fluorescence microscopy and analyzed at the single-cell level. Microscopy is also used to assign cells to different subpopulations based on differences in morphology or level of staining by molecular probes. The kinetic parameters obtained for individual cells are then averaged for different cell subpopulations and the mean values of these parameters are finally compared between subpopulations. To test our single-cell-kinetics approach, we studied MDR-related efflux for two subpopulations of cultured breast cancer cells: cells in 2N and 4N phases of the cell cycle. The assignment of cells to 2N and 4N subpopulations was done by fluorescent DNA staining after the completion of efflux. By using the single-cell-kinetics approach, we were able to prove for the first time that the rates of MDR-related efflux differ in 2N and 4N phases of the cell cycle. We foresee that this approach will be an important tool in studies of MDR and in designing combination chemotherapies.

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ABC Proteins and Oncology: Expression, Detection, and Implication of ABC Proteins in Solid Tumors

Cited by 5 publications

References 117 publications

Temporal dynamics of the ABC transporter response to insecticide treatment: insights from the malaria vector Anopheles stephensi

Temporal dynamics of the ABC transporter response to insecticide treatment: insights from the malaria vector Anopheles stephensi

Kinetics of MDR Transport in Tumor-Initiating Cells

Single-Cell-Kinetics Approach to Compare Multidrug Resistance-Associated Membrane Transport in Subpopulations of Cells

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