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Changes in Gene Expression Profile in two Multidrug Resistant Cell Lines derived from a same Drug Sensitive Cell line

ABSTRACT: Resistance to chemotherapy is one of the most relevant aspects of treatment failure in cancer. Cell lines are used as models to study resistance. We analyze the transcriptional profile of two multidrug resistant (MDR) cell lines (Lucena 1 and FEPS) derived from the same drug-sensitive cell K562. Microarray data identified 130 differentially expressed genes (DEG) between K562 vs Lucena, 1,932 between K562 vs FEPS, and 1,211 between Lucena 1 versus FEPS. The NOTCH pathway was affected in FEPS with overexpression of NOTCH2 and HEY1. The highly overexpressed gene in MDR cell was ABCB1, and both presented the ABCB1 promoter unmethylated.

ORGANISM(S): Homo sapiens

PROVIDER: GSE57470 | GEO | 2015/01/01

SECONDARY ACCESSION(S): PRJNA246521

REPOSITORIES: GEO

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Changes in Gene Expression Profile in two Multidrug Resistant Cell Lines derived from a same Drug Sensitive Cell line

Project description:Resistance to chemotherapy is one of the most relevant aspects of treatment failure in cancer. Cell lines are used as models to study resistance. We analyze the transcriptional profile of two multidrug resistant (MDR) cell lines (Lucena 1 and FEPS) derived from the same drug-sensitive cell K562. Microarray data identified 130 differentially expressed genes (DEG) between K562 vs Lucena, 1,932 between K562 vs FEPS, and 1,211 between Lucena 1 versus FEPS. The NOTCH pathway was affected in FEPS with overexpression of NOTCH2 and HEY1. The highly overexpressed gene in MDR cell was ABCB1, and both presented the ABCB1 promoter unmethylated. Gene expression profiles were obtained with the GeneChip® Human Genome U133 Plus 2.0 Array (Affymetrix, Singapore) according to the manufacturer´s instructions; all hybridization experiments were carried out in duplicate. The following samples were analyzed: human K562 cell line RNA from cells grown without drugs; human Lucena 1 cell line RNA from cells grown in medium with vincristine (Lucena 1+VCR); Lucena 1 cell line RNA from cells grown in medium without drugs (Lucena 1-VCR); human FEPS cell line RNA from cells grown in medium with daunorubicin (FEPS +DNR), and FEPS cell line RNA from cells grown in medium without drugs (FEPS -DNR).Comparisons of microarray expression data were carried out between K562 vs Lucena 1 grown in medium without vincristine; K562 vs FEPS grown in medium without daunorubicin; Lucena 1 grown in medium without vincristine vs FEPS grown in medium without daunorubicin. Additionally, we compared expression profiles of each multidrug resistant cell line (Lucena 1 and FEPS) grown in different conditions: Lucena 1 grown in medium without vincristine vs Lucena 1 grown in medium with vincristine, and FEPS grown in medium without daunorubicin vs FEPS grown in medium with daunorubicin.

2015-01-01 | E-GEOD-57470 | biostudies-arrayexpress

Targeting mitochondrial translation overcomes multidrug resistance in FBXW7-deficient cells

Project description:FBXW7 is one of the most frequently mutated tumor suppressors, the deficiency of which has been associated with resistance to some anticancer therapies. Through bioinformatic analyses and genome-wide CRISPR screens, we here reveal that FBXW7 deficiency leads to multi-drug resistance (MDR), to a bigger extent than well-established MDR-drivers such as ABCB1. Proteomic data from FBXW7-deficient cells and human cancer samples identify the upregulation of mitochondrial function as a hallmark of FBXW7 deficiency, which has been previously linked to an increased resistance to chemotherapy. Accordingly, genetic or chemical targeting of mitochondria is preferentially toxic for FBXW7-deficient cells. For instance, targeting mitochondrial translation with the antibiotic Tigecycline efficiently kills FBXW7-deficient cells in vitro and in vivo, by a mechanism that involves activation of the Integrated Stress Response (ISR). Searching for additional drugs that overcome MDR in FBXW7-deficient cells, we found several targeted therapies such as Erlotinib, Dasatinib or Vemurafenib which unexpectedly also activate the ISR. Together, our study reveals that one of the most frequent mutations in cancer reduces the sensitivity to the vast majority of available therapies, and identifies a general principle to overcome such resistance.

2022-06-08 | PXD029981 | Pride

Changes in the expression of miR-381 and miR-495 are inversely associated with the expression of the MDR1 gene and development of multi-drug resistance

Project description:Multidrug resistance (MDR) frequently develops in cancer patients exposed to chemotherapeutic agents and is usually brought about by over-expression of P-glycoprotein (P-gp) which acts as a drug efflux pump. MiRNAome profiling using next-generation sequencing identified differentially expressed microRNAs (miRs) between parental K562 cells and MDR K562 cells (K562/ADM) induced by chronic adriamycin treatment. MiRNAome profiling in untreated K562 cells and K562 cells exposed to long-term adriamycin treatment

2013-10-29 | E-GEOD-51774 | biostudies-arrayexpress

Changes in the expression of miR-381 and miR-495 are inversely associated with the expression of the MDR1 gene and development of multi-drug resistance

2013-10-29 | GSE51774 | GEO

Multidrug Resistance-Linked Gene Signature Predicts Overall Survival of Patients with Primary Ovarian Serous Carcinoma

Project description:This study assesses the ability of multidrug resistance (MDR)-associated gene expression patterns to predict survival in patients with newly diagnosed carcinoma of the ovary. The scope of this research differs substantially from that of previous reports, as a very large set of genes was evaluated whose expression has been shown to affect response to chemotherapy. We applied a customized TaqMan Low-Density Array, a highly sensitive and specific assay, to study the expression profiles of 380 MDR-linked genes in 80 tumor specimens collected at initial surgery to debulk primary serous carcinoma of Mullerian origin. The RNA expression profiles of these drug resistance genes were correlated with clinical outcomes.

2012-04-19 | E-GEOD-30009 | biostudies-arrayexpress

Genetic changes in the evolution of multidrug resistance for cultured human ovarian cancer cells

Project description:Gene expression profiles were assessed for vincristine-sensitive parental ovarian tumor cell line (SKOV3) and its highly vincristine-resistant derivative (SKVCR 2.0) Keywords: vincristine, drug resistance, ovarian, SKOV3, MDR

2007-08-24 | GSE7556 | GEO

Tepoxalin increases chemotherapy efficacy in drug-resistant breast cancer cells overexpressing the multidrug transporter gene ABCB1

Project description:Efficacious cancer chemotherapeutic treatment requires both therapy delivery and retention by malignant cells. Cancer cell overexpression of the multidrug transmembrane transporter gene ABCB1 thwarts therapy retention, leading to a drug-resistant phenotype. We explored the phenotypic impact of ABCB1 overexpression in normal human mammary epithelial cells (HMECs) via acute adenoviral delivery and in breast cancer cell lines with stable integration of inducible ABCB1 expression. One hundred sixty-two genes were differentially expressed between ABCB1-expressing and GFP-expressing HMECs, including the gene encoding the cyclooxygenase-2 protein, PTGS2. Several breast cancer cell lines with inducible ABCB1 expression demonstrated sensitivity to the 5-lipoxygenase, cyclooxygenase-1/2 inhibitor tepoxalin in two-dimensional drug response assays, and combination treatment of tepoxalin either with chemotherapies or with histone deacetylase (HDAC) inhibitors improved therapeutic efficacy in these lines. Moreover, selection for the ABCB1-expressing cell population was reduced in three-dimensional co-cultures of ABCB1-expressing and GFP-expressing cells when chemotherapy was given in combination with tepoxalin. Further study is warranted to ascertain the clinical potential of tepoxalin, an FDA-approved therapeutic for use in domesticated mammals, to restore chemosensitivity and improve drug response in patients with ABCB1-overexpressing drug-resistant breast cancers.

2021-08-04 | GSE173411 | GEO

Gene Expression Pattern in EP300 knocked-down MCF7 cells and corresponding paclitaxel resistant derivatives

Project description:EP300, a transcriptional co-activator of E-cadherin, has been recently found by our group to regulate doxorubicin resistance via by-pass of senescence and paclitaxel resistance by overcoming apoptosis in a minimally transformed mammary epithelial cells (MTMEC). Moreover, EP300 deleted MTMEC cells exhibit an multi-drug resistant (MDR) phenotype independent of P-glycoprotein (ABCB1), an efflux pump or ABC drug transporter. This whole transcriptome array study was undertaken in order to explore the downstream targets in the EP300-mediated drug resistance, epidermal-to-mesenchymal transition and cancer stem cell phenotypes in breast cancer cell line MCF7.

2017-06-13 | GSE76200 | GEO

Clinical Relevance of Multidrug Resistance Gene Expression in Ovarian Serous Carcinoma Effusions

Project description:The presence of tumor cells in effusions within serosal cavities is a clinical manifestation of advanced-stage cancer and is generally associated with poor survival. Identifying molecular targets may help to design efficient treatments to eradicate these aggressive cancer cells and improve patient survival. Using a state-of-the-art Taqman-based qRT-PCR assay, we investigated the multidrug resistance (MDR) transcriptome of 32 unpaired ovarian serous carcinoma effusion samples obtained at diagnosis or at disease recurrence following chemotherapy. MDR genes were selected a priori based on an extensive curation of the literature published during the last three decades. We found three gene signatures with a statistically significant correlation with overall survival (OS), response to treatment (complete response - CR vs. other), and progression free survival (PFS). The median log-rank p-values for the signatures were 0.023, 0.034, and 0.008, respectively. No correlation was found with residual tumor status after cytoreductive surgery, treatment (with or without chemotherapy) and stage defined according to the International Federation of Gynecology and Obstetrics. Further analyses demonstrated that gene expression alone can effectively predict the survival outcome of women with ovarian serous carcinoma (OS: log-rank p=0.0000 and PFS: log-rank p=0.002). Interestingly, the signature for overall survival is the same in patients at first presentation and those who had chemotherapy and relapsed. This pilot study highlights two new gene signatures that may help in optimizing the treatment for ovarian carcinoma patients with effusions.

2011-11-17 | GSE29702 | GEO

Multidrug Resistance-Linked Gene Signature Predicts Overall Survival of Patients with Primary Ovarian Serous Carcinoma

2012-04-19 | GSE30009 | GEO

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