Transcription Factor Differences in Cisplatin Resistant Cells
Acquired resistance frequently develops in humans after the initial use of cis-diamminedichloroplatinum(II) (CP). Furthermore, both clinical and laboratory results suggest tumor cells with resistance to CP are often cross resistant to other structurally and mechanistically distinct agents. For example, the human squamous cell carcinoma SCC25/CP, which has 12-fold acquired resistance to CP, is also approximately 7-fold resistant to methotrexate, 5-fold resistant to melphalan and 3-fold resistant to cyclophosphamide (Kelley et al., 1988). Studies with other cells suggest CP resistance can be associated with cross resistance to x-radiation in human tumor cell lines (Schwartz et al., 1988). Thus, brief or repeated exposure to CP can lead to cross resistance to other cancer therapeutics but the mechanism for the drug cross-resistance is not known. Moreover, the generation of anticancer drug cross-resistance is not unique to CP and can be seen with other agents. Because many anticancer agents are genotoxic, altered gene expression might occur after drug treatment. Indeed, increased gene expression is frequently seen in cells with acquired resistance to anticancer drugs. The focus of the work described in this manuscript has been to examine the mechanistic basis for alter gene expression in a human cell line with acquired resistance to CP.
KeywordsSCC26 Cell Drug Resistant Gene Human Squamous Cell Carcinoma Human Metallothionein Basal Regulatory Element
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