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• W2023129794 abstract "Resistance to cisplatin, one of the most widely used anticancer chemotherapeutic agents, is a major clinical problem. There is no effective way to predict development of cisplatin resistance in cancers. As determined by reverse transcription-polymerase chain reaction and Western blotting, the expression of gamma-catenin, an adherens junction protein, was decreased in KB-CP20 and 7404-CP20 cells compared with parental-sensitive cells. Short-term treatment with cisplatin of the parental cells resulted in proteolysis of gamma-catenin as evaluated in membrane pellet preparations, and the extent of cleavage increased as cisplatin concentration was raised from 1 to 5 microg/ml during 1 h of treatment. Uncleaved cytoplasmic gamma-catenin increased under the same conditions. These biochemical results were supported by confocal microscopy, which showed a loss of gamma-catenin from adherens plaques after cisplatin treatment. Cleavage of gamma-catenin was specific to cisplatin treatment in that cleavage did not occur after treatment with doxorubicin and cytosine arabinoside. Pretreatment of KB and 7404 cells with cisplatin for 1 h resulted in reduced uptake of [(14)C]carboplatin, suggesting that the biochemical changes induced by cisplatin treatment, including cleavage of gamma-catenin, could affect the ability of cells to internalize platinum compounds. Cells transfected with the gamma-catenin gene are sensitive to cisplatin compared with cells transfected with a control vector. Our data suggest that proteolysis and altered localization of gamma-catenin are early markers for the response of cells to cisplatin, and reduced levels of gamma-catenin in resistant cells may indicate an important role for gamma-catenin in mediating or modulating the toxicity of cisplatin in cancer cells." @default.
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• W2023129794 date "2004-04-20" @default.
• W2023129794 modified "2023-09-23" @default.
• W2023129794 title "Down-Regulation and Altered Localization of γ-Catenin in Cisplatin-Resistant Adenocarcinoma Cells" @default.
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• W2023129794 doi "https://doi.org/10.1124/mol.65.5.1217" @default.
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