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.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Liang XJ,Shen DW,Gottesman MMdoi
10.1124/mol.65.5.1217keywords:
subject
Has Abstractpub_date
2004-05-01 00:00:00pages
1217-24issue
5eissn
0026-895Xissn
1521-0111pii
65/5/1217journal_volume
65pub_type
杂志文章abstract：:It has long been believed that the cortical actin cytoskeleton plays an important role in regulating the secretion of hormones and neurotransmitters. In this study, we investigated the control of actin dynamics in primary neuroendocrine cells and determined the relationship of actin dynamics to various components of t...
journal_title：Molecular pharmacology
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journal_title：Molecular pharmacology
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abstract：:Carbachol is 100 times more potent for inhibiting cyclic AMP formation than for stimulating phosphoinositide (PI) hydrolysis in chick heart cells. To determine whether this reflects differences in agonist affinity of the receptor(s) coupled to the two responses, we measured these functional responses following removal...
journal_title：Molecular pharmacology
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journal_title：Molecular pharmacology
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journal_title：Molecular pharmacology
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1993-11-01 00:00:00
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journal_title：Molecular pharmacology
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更新日期：2003-11-01 00:00:00
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journal_title：Molecular pharmacology
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doi：
更新日期：1997-03-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1995-08-01 00:00:00
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pub_type： 杂志文章
doi：10.1124/mol.105.012401
更新日期：2005-10-01 00:00:00
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journal_title：Molecular pharmacology
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doi：
更新日期：1988-10-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1991-04-01 00:00:00
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journal_title：Molecular pharmacology
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doi：
更新日期：1995-03-01 00:00:00
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doi：
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journal_title：Molecular pharmacology
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doi：
更新日期：1993-12-01 00:00:00
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更新日期：2006-05-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1990-06-01 00:00:00
