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Transcriptional profiling of NCI/ADR-RES cells unveils a complex network of signaling pathways and molecular mechanisms of drug resistance.

ABSTRACT: Background:Ovarian cancer has the highest mortality rate among all the gynecological cancers. This is mostly due to the resistance of ovarian cancer to current chemotherapy regimens. Therefore, it is of crucial importance to identify the molecular mechanisms associated with chemoresistance. Methods:NCI/ADR-RES is a multidrug-resistant cell line that is a model for the study of drug resistance in ovarian cancer. We carried out a microarray-derived transcriptional profiling analysis of NCI/ADR-RES to identify differentially expressed genes relative to its parental OVCAR-8. Results:Gene-expression profiling has allowed the identification of genes and pathways that may be important for the development of drug resistance in ovarian cancer. The NCI/ADR-RES cell line has differential expression of genes involved in drug extrusion, inactivation, and efficacy, as well as genes involved in the architectural and functional reorganization of the extracellular matrix. These genes are controlled through different signaling pathways, including MAPK-Akt, Wnt, and Notch. Conclusion:Our findings highlight the importance of using orthogonal therapies that target completely independent pathways to overcome mechanisms of resistance to both classical chemotherapeutic agents and molecularly targeted drugs.

SUBMITTER: Vert A

PROVIDER: S-EPMC5757493 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Transcriptional profiling of NCI/ADR-RES cells unveils a complex network of signaling pathways and molecular mechanisms of drug resistance.

Vert Anna A Castro Jessica J Ribó Marc M Vilanova Maria M Benito Antoni A

OncoTargets and therapy 20180104

<h4>Background</h4>Ovarian cancer has the highest mortality rate among all the gynecological cancers. This is mostly due to the resistance of ovarian cancer to current chemotherapy regimens. Therefore, it is of crucial importance to identify the molecular mechanisms associated with chemoresistance.<h4>Methods</h4>NCI/ADR-RES is a multidrug-resistant cell line that is a model for the study of drug resistance in ovarian cancer. We carried out a microarray-derived transcriptional profiling analysis ...[more]

PMID: 29379303

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Project description:BackgroundShared dysregulated pathways may contribute to Parkinson's disease and type 2 diabetes, chronic diseases that afflict millions of people worldwide. Despite the evidence provided by epidemiological and gene profiling studies, the molecular and functional networks implicated in both diseases, have not been fully explored. In this study, we used an integrated network approach to investigate the extent to which Parkinson's disease and type 2 diabetes are linked at the molecular level.Methods and findingsUsing a random walk algorithm within the human functional linkage network we identified a molecular cluster of 478 neighboring genes closely associated with confirmed Parkinson's disease and type 2 diabetes genes. Biological and functional analysis identified the protein serine-threonine kinase activity, MAPK cascade, activation of the immune response, and insulin receptor and lipid signaling as convergent pathways. Integration of results from microarrays studies identified a blood signature comprising seven genes whose expression is dysregulated in Parkinson's disease and type 2 diabetes. Among this group of genes, is the amyloid precursor protein (APP), previously associated with neurodegeneration and insulin regulation. Quantification of RNA from whole blood of 192 samples from two independent clinical trials, the Harvard Biomarker Study (HBS) and the Prognostic Biomarker Study (PROBE), revealed that expression of APP is significantly upregulated in Parkinson's disease patients compared to healthy controls. Assessment of biomarker performance revealed that expression of APP could distinguish Parkinson's disease from healthy individuals with a diagnostic accuracy of 80% in both cohorts of patients.ConclusionsThese results provide the first evidence that Parkinson's disease and diabetes are strongly linked at the molecular level and that shared molecular networks provide an additional source for identifying highly sensitive biomarkers. Further, these results suggest for the first time that increased expression of APP in blood may modulate the neurodegenerative phenotype in type 2 diabetes patients.

Dataset Information

Transcriptional profiling of NCI/ADR-RES cells unveils a complex network of signaling pathways and molecular mechanisms of drug resistance.

Publications

Transcriptional profiling of NCI/ADR-RES cells unveils a complex network of signaling pathways and molecular mechanisms of drug resistance.

Similar Datasets

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