Transcriptomics

Dataset Information

31

Transcription profiling of six ovarian carcinoma cell lines exposed to docetaxel or paclitaxel


ABSTRACT: Each of the six ovarian carcinoma cell lines was exposed to docetaxel or paclitaxel at IC50 levels (the concentration required to kill 50% of the population). After several passages at this initial concentration of taxanes, drug concentrations were escalated, and this process was repeated until variants displayed at least a 10-fold resistance to the selecting agents. mRNA and genomic DNA were isolated from the parental and resistant variants, and hybridized onto Stanford human cDNA microarrays containing about 42000 elements. We analyzed the gene expression profiles and copy number alterations, and identified a cluster of genes co-activated with MDR1 on chromosome arm 7q21. In six of these variants, regional activation was driven by gene copy number alterations, with low-level gains or high-level amplifications spanning the involved region. However, three variants displayed a regional increases in gene expression even without concomitant gene copy number changes. These results suggest that regional gene activation may be a fundamental mechanism for acquired drug resistance, with or without changes in gene dosage. In addition to numerical and structural chromosomal changes driven by genome instability in cancer cells, other mechanisms might be involved in MDR1 regional activation, such as chromatin remodeling and DNA or histone modifications of the 7q21 region.

ORGANISM(S): Homo sapiens  

SUBMITTER: Janos Demeter  Yan Wang     

PROVIDER: E-SMDB-3612 | ArrayExpress| 2014-05-02

REPOSITORIES: ArrayExpress

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Publications

Regional activation of chromosomal arm 7q with and without gene amplification in taxane-selected human ovarian cancer cell lines.

Wang Yan C YC   Juric Dejan D   Francisco Brian B   Yu Ron X RX   Duran George E GE   Chen G Kevin GK   Chen Xin X   Sikic Branimir I BI  

Genes, chromosomes & cancer 20060401 4


Taxanes are important drugs in the treatment of ovarian and other cancers, but their efficacy is limited by intrinsic and acquired drug resistance. Expression of the multidrug transporter P-glycoprotein, encoded by the MDR1 (ABCB1) gene, is one of the causes of clinical drug resistance to taxanes. To study the mechanisms of MDR1 activation related to taxanes, we established 11 multidrug-resistant variants from six ovarian cancer cell lines by continuous exposure to either paclitaxel or docetaxel  ...[more]

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