Transcriptomics

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Gene expression changes with induction of in-vitro platinum-resistance in ovarian cancer cell lines.


ABSTRACT: We treated 8 human ovarian cancer cell lines with cisplatin in treatment/recovery cycles to induce in-vitro resistance to the drug. Microarrays measured gene expression at baseline and after each dose schedule (after recovery). OVCA cells lines (T8, OVCAR5, OV2008, IGROV1, C13, A2780S, A2780CP, and A2008) were used in the study. Cells were subject to sequential treatment with increasing doses of cis-diammine-dichloroplatinum (cisplatin, CIS), using three dosing schedules resulting in a total of 144 treatment/expansion cycles. Treatment schedules A, B and C included three treatments with 1, 2 and 3μg/ml CIS respectively, followed by three treatments with 3, 4 and 5μg/ml, respectively. Each CIS-treatment was followed by a cell recovery/expansion phase. Both CIS-resistance and genome-wide expression changes were measured serially in each cell line at baseline and after 3 and 6 CIS-treatment/expansion cycles. CIS-resistance was quantified using CellTiter-96, MTS proliferation assays (Fisher Scientific) and genome-wide expression was performed using Affymetrix Human U133 Plus 2.0 GeneChips as previously described.

ORGANISM(S): Homo sapiens  

SUBMITTER: Johnathan Lancaster   Douglas Marchion  Steven Eschrich 

PROVIDER: E-GEOD-23553 | ArrayExpress | 2011-10-02

SECONDARY ACCESSION(S): GSE23553PRJNA133363

REPOSITORIES: GEO, ArrayExpress

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Publications


Despite initial sensitivity to chemotherapy, ovarian cancers (OVCA) often develop drug resistance, which limits patient survival. Using specimens and/or genomic data from 289 patients and a panel of cancer cell lines, we explored genome-wide expression changes that underlie the evolution of OVCA chemoresistance and characterized the BCL2 antagonist of cell death (BAD) apoptosis pathway as a determinant of chemosensitivity and patient survival.Serial OVCA cell cisplatin treatments were performed  ...[more]

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