Mechanisms of drug resistance in ovarian cancer

National Institute On Aging

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Abstract

Using ovarian cancer cell line OV90 as a starting line, we have developed a series of lines individually resistant to 3 different drugs (cisplatin, doxorubicin and paclitaxel). Three independent clones for each resistant phenotype was obtained, giving us a total of 9 cell lines for comparison to the parental cells (3 cisplatin resistant clones OV90C, 3 doxorubicin resistant clones OV90D, and 3 paclitaxel resistant clones OV90P). We have used Illumina microarrays to analyze gene expression of these clones and have identified genes differentially expressed in the various drug resistance phenotypes. Interestingly, we have identified several genes that are common to several resistance types. For example, ABCB1 and GAGE genes were consistently elevated in resistant cells, while PRSS8 and MSMB1 were consistently downregulated. We are currently validating these and other candidate genes by quantitative RT-PCR in these cell lines. We are also planning to validate these genes in patient tissues using RT-PCR and immunohistochemistry.