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Decreased [18 F]fluoro-2-deoxy- d -glucose incorporation and increased glucose transport are associated with resistance to 5FU in MCF7 cells in vitro

Abstract Introduction Tumor refractoriness to chemotherapy is frequently due to the acquisition of resistance. Resistant cells selected by exposure to chemotherapy agents may exhibit differences in [18 F]fluoro-2-deoxy- d -glucose (FDG) incorporation, as compared with sensitive cells. Methods FDG in...

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Published in:Nuclear medicine and biology 2007-11, Vol.34 (8), p.955-960
Main Authors: Smith, Tim A.D, Sharma, Rituka I, Wang, Weiguang G, Welch, Andy E, Schweiger, Lutz F, Collie-Duguid, Elaina S.R
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container_title Nuclear medicine and biology
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creator Smith, Tim A.D
Sharma, Rituka I
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Collie-Duguid, Elaina S.R
description Abstract Introduction Tumor refractoriness to chemotherapy is frequently due to the acquisition of resistance. Resistant cells selected by exposure to chemotherapy agents may exhibit differences in [18 F]fluoro-2-deoxy- d -glucose (FDG) incorporation, as compared with sensitive cells. Methods FDG incorporation, hexokinase (HK) activity, glucose transport and ATP content were determined in clones of 5-fluorouracil (5FU)-resistant MCF7 cells, established by long-term exposure to increasing 5FU concentrations, and in parental MCF7 cells. Results FDG incorporation was decreased in MCF7 cells resistant to 5FU; HK activity was similar in the resistant and sensitive cells, while glucose transport was increased, as compared with sensitive cells. Treatment of cells with the glucose efflux inhibitor phloretin increased FDG incorporation to similar levels in the resistant and sensitive cells. Analysis of microarray data demonstrated the expression of GLUT1, 8 and 10 transporters in MCF7 cells. GLUT8 and 10 expression was decreased in the resistant cells, while GLUT1 was only increased in cells resistant to the lowest 5FU concentration. Conclusion FDG incorporation in 5FU-resistant MCF7 cells is decreased, as compared with sensitive cells. Our findings also suggest that this may be due to high rates of membrane glucose transport in the resistant cells resulting in enhanced efflux of FDG. We believe that this is the first demonstration that facilitative glucose transporters can actually decrease the incorporation of FDG.
doi_str_mv 10.1016/j.nucmedbio.2007.07.007
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Resistant cells selected by exposure to chemotherapy agents may exhibit differences in [18 F]fluoro-2-deoxy- d -glucose (FDG) incorporation, as compared with sensitive cells. Methods FDG incorporation, hexokinase (HK) activity, glucose transport and ATP content were determined in clones of 5-fluorouracil (5FU)-resistant MCF7 cells, established by long-term exposure to increasing 5FU concentrations, and in parental MCF7 cells. Results FDG incorporation was decreased in MCF7 cells resistant to 5FU; HK activity was similar in the resistant and sensitive cells, while glucose transport was increased, as compared with sensitive cells. Treatment of cells with the glucose efflux inhibitor phloretin increased FDG incorporation to similar levels in the resistant and sensitive cells. Analysis of microarray data demonstrated the expression of GLUT1, 8 and 10 transporters in MCF7 cells. GLUT8 and 10 expression was decreased in the resistant cells, while GLUT1 was only increased in cells resistant to the lowest 5FU concentration. Conclusion FDG incorporation in 5FU-resistant MCF7 cells is decreased, as compared with sensitive cells. Our findings also suggest that this may be due to high rates of membrane glucose transport in the resistant cells resulting in enhanced efflux of FDG. 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Resistant cells selected by exposure to chemotherapy agents may exhibit differences in [18 F]fluoro-2-deoxy- d -glucose (FDG) incorporation, as compared with sensitive cells. Methods FDG incorporation, hexokinase (HK) activity, glucose transport and ATP content were determined in clones of 5-fluorouracil (5FU)-resistant MCF7 cells, established by long-term exposure to increasing 5FU concentrations, and in parental MCF7 cells. Results FDG incorporation was decreased in MCF7 cells resistant to 5FU; HK activity was similar in the resistant and sensitive cells, while glucose transport was increased, as compared with sensitive cells. Treatment of cells with the glucose efflux inhibitor phloretin increased FDG incorporation to similar levels in the resistant and sensitive cells. Analysis of microarray data demonstrated the expression of GLUT1, 8 and 10 transporters in MCF7 cells. GLUT8 and 10 expression was decreased in the resistant cells, while GLUT1 was only increased in cells resistant to the lowest 5FU concentration. Conclusion FDG incorporation in 5FU-resistant MCF7 cells is decreased, as compared with sensitive cells. Our findings also suggest that this may be due to high rates of membrane glucose transport in the resistant cells resulting in enhanced efflux of FDG. 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Resistant cells selected by exposure to chemotherapy agents may exhibit differences in [18 F]fluoro-2-deoxy- d -glucose (FDG) incorporation, as compared with sensitive cells. Methods FDG incorporation, hexokinase (HK) activity, glucose transport and ATP content were determined in clones of 5-fluorouracil (5FU)-resistant MCF7 cells, established by long-term exposure to increasing 5FU concentrations, and in parental MCF7 cells. Results FDG incorporation was decreased in MCF7 cells resistant to 5FU; HK activity was similar in the resistant and sensitive cells, while glucose transport was increased, as compared with sensitive cells. Treatment of cells with the glucose efflux inhibitor phloretin increased FDG incorporation to similar levels in the resistant and sensitive cells. Analysis of microarray data demonstrated the expression of GLUT1, 8 and 10 transporters in MCF7 cells. GLUT8 and 10 expression was decreased in the resistant cells, while GLUT1 was only increased in cells resistant to the lowest 5FU concentration. Conclusion FDG incorporation in 5FU-resistant MCF7 cells is decreased, as compared with sensitive cells. Our findings also suggest that this may be due to high rates of membrane glucose transport in the resistant cells resulting in enhanced efflux of FDG. We believe that this is the first demonstration that facilitative glucose transporters can actually decrease the incorporation of FDG.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>17998098</pmid><doi>10.1016/j.nucmedbio.2007.07.007</doi><tpages>6</tpages></addata></record>
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subjects Biological Transport, Active - drug effects
Breast Neoplasms - diagnostic imaging
Breast Neoplasms - metabolism
Cell Line, Tumor
Drug Resistance, Neoplasm
FDG
Fluorodeoxyglucose F18 - pharmacokinetics
Fluorouracil - administration & dosage
Glucose - metabolism
Glucose transport
Humans
MCF7 cells
Metabolic Clearance Rate - drug effects
Radiology
Radionuclide Imaging
Radiopharmaceuticals - pharmacokinetics
title Decreased [18 F]fluoro-2-deoxy- d -glucose incorporation and increased glucose transport are associated with resistance to 5FU in MCF7 cells in vitro
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