ArticleMolecular cancer2010
Blocking of ERK1 and ERK2 sensitizes human mesothelioma cells to doxorubicin.
Article in Molecular cancer, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 78 citations in OpenAlex.
- Advances in the Basic Sciences in Thoracic Oncology in the Last 20 Years and Their Translational Impact.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2026Review
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- Design, synthesis, and cytotoxicity of ibuprofen-appended benzoxazole analogues against human breast adenocarcinoma.RSC medicinal chemistry · 2024Article
- Effect of quercetin on doxorubicin cytotoxicity in sensitive and resistant human MCF7 breast cancer cell lines.Biomedical reports · 2024Article
- TonEBP/NFAT5 expression is associated with cisplatin resistance and migration in macrophage-induced A549 cells.BMC molecular and cell biology · 2024Article
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- Titanium dioxide nanostructure-loaded Adriamycin surmounts resistance in breast cancer therapy: ABCA/P53/C-myc crosstalk.Future science OA · 2024Article
- Thymoquinone Nanoparticle Induces Apoptosis and Cell Migration Retardation through Modulating of SUMOylation Process Genes in Breast Cancer Cell Line.Iranian journal of biotechnology · 2024Article
- Integrin α6β4 Confers Doxorubicin Resistance in Cancer Cells by Suppressing Caspase-3-Mediated Apoptosis: Involvement of N-Glycans on β4 Integrin Subunit.Biomolecules · 2023Article
- Single-Cell Proliferation Microfluidic Device for High Throughput Investigation of Replicative Potential and Drug Resistance of Cancer Cells.Cellular and molecular bioengineering · 2023Article
- Article
- Prolactin-induced protein (PIP) increases the sensitivity of breast cancer cells to drug-induced apoptosis.Scientific reports · 2023Article
- MEK1 drives oncogenic signaling and interacts with PARP1 for genomic and metabolic homeostasis in malignant pleural mesothelioma.Cell death discovery · 2023Article
- Extracellular Vesicles Isolated from Malignant Mesothelioma Cancer-Associated Fibroblasts Induce Pro-Oncogenic Changes in Healthy Mesothelial Cells.International journal of molecular sciences · 2022Article
- Transglutaminase 2 enhances hepatocyte growth factor signaling to drive the mesothelioma cancer cell phenotype.Molecular carcinogenesis · 2022Article
- Identification of ABCA5 among ATP-Binding Cassette Transporter Family as a New Biomarker for Colorectal Cancer.Journal of oncology · 2022Article
- CXCR2 Small-Molecule Antagonist Combats Chemoresistance and Enhances Immunotherapy in Triple-Negative Breast Cancer.Frontiers in pharmacology · 2022Article
- Knowledge, Vaccination Status, and Reasons for Avoiding Vaccinations against Hepatitis B in Developing Countries: A Systematic Review.Vaccines · 2021Review
- Transcriptomic alterations in malignant pleural mesothelioma cells in response to long‑term treatment with bullfrog sialic acid‑binding lectin.Molecular medicine reports · 2021Article
- Mechanisms of doxorubicin-induced drug resistance and drug resistant tumour growth in a murine breast tumour model.BMC cancer · 2019Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundMalignant mesotheliomas (MM) have a poor prognosis, largely because of their chemoresistance to anti-cancer drugs such as doxorubicin (Dox). Here we show using human MM lines that Dox activates extracellular signal-regulated kinases (ERK1 and 2), causally linked to increased expression of ABC transporter genes, decreased accumulation of Dox, and enhanced MM growth. Using the MEK1/2 inhibitor, U0126 and stably transfected shERK1 and shERK2 MM cell lines, we show that inhibition of both ERK1 and 2 sensitizes MM cells to Dox.
resultsU0126 significantly modulated endogenous expression of several important drug resistance (BCL2, ABCB1, ABCC3), prosurvival (BCL2), DNA repair (BRCA1, BRCA2), hormone receptor (AR, ESR2, PPARγ) and drug metabolism (CYP3A4) genes newly identified in MM cells. In comparison to shControl lines, MM cell lines stably transfected with shERK1 or shERK2 exhibited significant increases in intracellular accumulation of Dox and decreases in cell viability. Affymetrix microarray analysis on stable shERK1 and shERK2 MM lines showed more than 2-fold inhibition (p ≤ 0.05) of expression of ATP binding cassette genes (ABCG1, ABCA5, ABCA2, MDR/TAP, ABCA1, ABCA8, ABCC2) in comparison to shControl lines. Moreover, injection of human MM lines into SCID mice showed that stable shERK1 or shERK2 lines had significantly slower tumor growth rates in comparison to shControl lines after Dox treatment.
conclusionsThese studies suggest that blocking ERK1 and 2, which play critical roles in multi-drug resistance and survival, may be beneficial in combination with chemotherapeutic drugs in the treatment of MMs and other tumors.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.