Involvement of EGFR in the promotion of malignant properties in multidrug resistant breast cancer cells

Xu, Jiawen; Li, Qingquan; Tao, Lili; Cheng, Yuanyuan; Yu, Juan; Chen, Qi; Liu, Xiuping; Xu, Zu-De

doi:10.3892/ijo.2011.1143

Cited by 27 publications

(35 citation statements)

References 23 publications

(26 reference statements)

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“…For example, incubation of human-derived PancCa tumor cell lines with standard of care agents such as gemcitabine, 5-fluorouracil, and cisplatin results in an elevation of MDR protein expression in surviving cells [4] and MDR-based resistance to frontline agents in breast cancer therapy is a well-established fact [5, 6]. One clinical strategy to overcome MDR is to co-administer inhibitors of MDR transport with the objective of increasing intracellular concentrations of the chemotherapeutic agents and achieving required therapeutic exposure [27].…”

Section: Discussionmentioning

confidence: 99%

“…MDR contributes to the poor response to frontline treatment of PancCA [3], as enhanced expression of MRP-1, MRP-3 and MRP-5 has been associated with resistance to gemcitabine and 5-fluorouracil [4]. In the treatment of breast cancer, over 80% of the breast cancer patients who receive chemotherapy will relapse with the eventual development of MDR disease primarily associated with overexpression of Pgp, MRP1 and BCRP [5, 6]. …”

Section: Introductionmentioning

confidence: 99%

“…The expression of the MDR phenotype in tumors has been linked to activation of the epidermal growth factor receptor (EGFR) and the subsequent downstream increase in ERK1/2 phosphorylation (p-ERK), which contributes to increased MDR-related protein expression [5, 7, 8]. Cellular proliferation and MDR have also been associated with increased expression of β-catenin and hypoxia-inducible factor 1α (HIF-1α) [9-11].…”

Section: Introductionmentioning

confidence: 99%

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Selective GPR55 antagonism reduces chemoresistance in cancer cells

Singh

Bernier

Wainer

2016

Pharmacological Research

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G protein-coupled receptor 55 (GPR55) possesses pro-oncogenic activity and its function can be competitively inhibited with (R,R’)-4’-methoxy-1-naphthylfenoterol (MNF) through poorly defined signaling pathways. Here, the anti-tumorigenic effect of MNF was investigated in the human pancreatic cancer cell line, PANC-1, by focusing on the expression of known cancer biomarkers and the expression and function of multidrug resistance (MDR) exporters such as P-glycoprotein (Pgp) and breast cancer resistance protein (BCRP). Incubation of PANC1 cells with MNF (1μM) for 24 h significantly decreased EGF receptor, pyruvate kinase M2 (PKM2), and β-catenin protein levels and was accompanied by significant reduction in nuclear accumulation of HIF-1α and the phospho-active forms of PKM2 and β-catenin. Inhibition of GPR55 with either MNF or the GPR55 antagonist CID 16020046 lowered the amount of MDR proteins in total cellular extracts while diminishing the nuclear expression of Pgp and BCRP. There was significant nuclear accumulation of doxorubicin in PANC-1 cells treated with MNF and the pre-incubation with MNF increased the cytotoxicity of doxorubicin and gemcitabine in these cells. Potentiation of doxorubicin cytotoxicity by MNF was also observed in MDA-MB-231 breast cancer cells and U87MG glioblastoma cells, which express high levels of GPR55. The data suggest that inhibition of GPR55 activity produces antitumor effects via attenuation of the MEK/ERK and PI3K-AKT pathways leading to a reduction in the expression and function of MDR proteins.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Selective GPR55 antagonism reduces chemoresistance in cancer cells

Singh

Bernier

Wainer

2016

Pharmacological Research

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“…This integrative approach has been, however, less widely used in inflammatory models. For IBD [64] and many other autoimmune diseases including Sjogren’s disease [65], we are still at the stage of documenting differential expression levels of miRNAs between disease and control cohorts.…”

Section: Transcriptomicsmentioning

confidence: 99%

Omics Approaches to Identify Potential Biomarkers of Inflammatory Diseases in the Focal Adhesion Complex

Brooks

Watson

Korcsmáros

2017

Genomics, Proteomics &Amp; Bioinformatics

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Inflammatory diseases such as inflammatory bowel disease (IBD) require recurrent invasive tests, including blood tests, radiology, and endoscopic evaluation both to diagnose and assess disease activity, and to determine optimal therapeutic strategies. Simple ‘bedside’ biomarkers could be used in all phases of patient management to avoid unnecessary investigation and guide further management. The focal adhesion complex (FAC) has been implicated in the pathogenesis of multiple inflammatory diseases, including IBD, rheumatoid arthritis, and multiple sclerosis. Utilizing omics technologies has proven to be an efficient approach to identify biomarkers from within the FAC in the field of cancer medicine. Predictive biomarkers are paving the way for the success of precision medicine for cancer patients, but inflammatory diseases have lagged behind in this respect. This review explores the current status of biomarker prediction for inflammatory diseases from within the FAC using omics technologies and highlights the benefits of future potential biomarker identification approaches.

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“…Therefore, the development of gene-targeted therapy for breast cancer requires further attention. Previous studies have revealed that numerous genes are involved in the occurrence and development of breast cancer, including cyclin D1, matrix metalloproteinases (MMPs) and E-cadherin (5)(6)(7)(8). Astrocyte elevated gene-1 (AEG1) has also been investigated with respect to poor prognosis in breast cancer (9).…”

Section: Introductionmentioning

confidence: 99%

Astrocyte elevated gene-1 promotes the proliferation and invasion of breast cancer cells by activating the Wnt/β-catenin signaling pathway

Dai

Wang

et al. 2017

Oncology Letters

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Abstract. Astrocyte elevated gene-1 (AEG1) was identified to be overexpressed in breast cancer, and to be associated with the development of breast cancer. In the present study, AEG1 was identified as highly expressed in the MCF-7, MDA-MB-231 and SK-BR-3 breast cancer cell lines and was detected in the MCF-10A normal breast epithelial cell line. The present study established an AEG1-knockdown MCF-7 cell line to investigate the expression status of certain cancer-associated proteins. Western blotting demonstrated that AEG1 may affect cancer cell proliferation and invasion via activating the Wnt/β-catenin signaling pathway, a hypothesis that has been supported by cell function tests. The results of the present study demonstrated that when AEG1 was significantly overexpressed in breast cancer cells it promoted cell proliferation and invasion via activating the Wnt/β-catenin signaling pathway. Therefore, AEG1 may serve as a novel therapeutic target in breast cancer. IntroductionBreast cancer is a common type of malignancy; the incidence of the disease has increased in recent years worldwide, currently ranking first with respect to cancer-associated morbidity in women (1-3). The traditional methods of treatment include surgery, radiotherapy and chemotherapy for patients with advanced breast cancer exhibit poor efficacy (4). Therefore, the development of gene-targeted therapy for breast cancer requires further attention. Previous studies have revealed that numerous genes are involved in the occurrence and development of breast cancer, including cyclin D1, matrix metalloproteinases (MMPs) and E-cadherin (5-8). Astrocyte elevated gene-1 (AEG1) has also been investigated with respect to poor prognosis in breast cancer (9). AEG1 is a potentially crucial mediator of tumor malignancy and a key converging point of a complex network of oncogenic signaling pathways (10-12). Previous studies revealed that the AEG1 gene was significantly overexpressed in a number of types of malignant cells, and is associated with tumorigenesis, proliferation, invasion and metastasis (13,14). Statistics also demonstrated that AEG1 was upregulated in breast cancer tissue and positively correlated with clinical stage and lymph node metastasis (15).The Wnt signaling pathway is one of the most important intracellular signal transduction pathways, and it affects the activated state of multiple effector molecules downstream (16)(17)(18)(19). It is closely associated with a variety of human tumor developments, and serves an important role in breast cancer cell proliferation and invasion (20,21). However, the mechanisms that underlie the activation of the Wnt signaling pathway in various types of breast cancer have yet to be identified. β-catenin has been revealed as a central regulator in the Wnt signaling pathway, and is associated with disease progression and poor prognosis in breast cancer (22). Typically, during activation of the Wnt signaling pathway, β-catenin accumulates in the cytosol at high levels, binds to T-cell factor/lymphoid enhancer fac...

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Involvement of EGFR in the promotion of malignant properties in multidrug resistant breast cancer cells

Cited by 27 publications

References 23 publications

Selective GPR55 antagonism reduces chemoresistance in cancer cells

Selective GPR55 antagonism reduces chemoresistance in cancer cells

Omics Approaches to Identify Potential Biomarkers of Inflammatory Diseases in the Focal Adhesion Complex

Astrocyte elevated gene-1 promotes the proliferation and invasion of breast cancer cells by activating the Wnt/β-catenin signaling pathway

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