The regulation effect of EGFR signaling pathway on PD-L1 expression on esophageal squamous cell carcinoma cell lines.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15577-e15577
Author(s):  
Ran Lin Wang ◽  
Tao Li ◽  
Jianming Huang ◽  
Jiahua Lv
Keyword(s):  
Mrna Expression ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Egfr Signaling ◽  
Egfr Signaling Pathway ◽  
Radiotherapy Alone ◽  
Pcr Method ◽  
Egfr Tki

e15577 Background: To explore the effect of radiation combined with Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors (EGFR-TKI) on the expression of PD-L1 in ESCC cell lines, and to provide theoretical support for radiotherapy combined with EGFR-TKI for esophageal cancer. Methods: Reverse transcription-polymerase chain reaction (RT-PCR) method was used to assess EGFR and PD-L1 mRNA expression on ESCC cell lines when different doses of X-ray irradiation were conducted on ESCC cell lines TE-1 and ECA-109 combining with EGFR-TKI or not. Results: In ESCC cell lines TE-1 and ECA-109, the expression of EGFR and PD-L1 mRNA was increased significantly by the activation of EGFR signaling pathway and decreased after the use of gefitinib (P > 0.01). Both EGFR (P < 0.01) and PD-L1(P < 0.01) mRNA expression of ESCC cell lines TE-1 and ECA-109 were increased by radiotherapy alone. EGFR-TKI could block the increase of both EGFR mRNA (P < 0.01) and PD-L1 mRNA (P < 0.01) which was induced by radiation. Conclusions: EGFR signaling pathway is involved in the regulation of PD-L1 expression in ESCC cell lines. Radiation could up-regulate the expression of EGFR and PD-L1 mRNA in ESCC cells which could be blocked by the use of EGFR-TKI.

scholarly journals Progress toward resistance mechanism to epidermal growth factor receptor tyrosine kinase inhibitor

2016 ◽  
Vol 11 (1) ◽  
pp. 427-431
Author(s):  
Lingling Zhang ◽  
Xiaoxue Zhang ◽  
Liang Zhao
Keyword(s):  
Drug Resistance ◽  
Epidermal Growth Factor Receptor ◽  
Signaling Pathway ◽  
Receptor Tyrosine Kinase ◽  
Kinase Inhibitor ◽  
Growth Factor Receptor ◽  
Egfr Signaling ◽  
Egfr Signaling Pathway ◽  
Epidermal Growth ◽  
Egfr Tki

AbstractThe EGFR signaling pathway plays an important role in the occurrence and development of many malignant tumors. It has become a hot spot in the treatment of advanced cancer. At present, the small molecule epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), has been shown to advanced non-small-cell lung cancer (NSCLC), has a marked drug resistance or has developed one. The EGFR signaling pathway regulates a variety of cellular functions, and its drug resistance may be related to a number of signal transduction pathways, including drug resistance mutations, structural activation, downstream signaling pathway activation and VEGF expression changes, and so on. In this paper, we review the production mechanism of EGFR-TKI drug resistance.

The ERB family receptor dimerization in glioblastoma—An eTag assay analysis of 23 cases

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 1582-1582
Author(s):  
M. R. Hameed ◽  
L. Sharer ◽  
E. Cho ◽  
S. Aisner ◽  
L. Cao ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Driving Forces ◽  
Growth Factor Receptor ◽  
Signaling Molecules ◽  
Egfr Signaling ◽  
Fluorescent Reporter ◽  
Downstream Signaling ◽  
Egfr Signaling Pathway ◽  
Ffpe Tumor ◽  
Her 2

1582 Background: Glioblastoma is the most malignant astrocytic tumor and accounts for about 50–60% of all astrocytic neoplasms. Despite intensive radiation and chemotherapy, less than 2% of patients survive more than 3 years. The Erb family of signaling molecules are transmembrane receptors with intrinsic kinase activity (except ErbB3) capable of modifying tyrosine residues on the receptor itself as well as on downstream signaling molecules. Under physiological conditions a variety of ligands interact and act as driving forces in the formation of homo and heterodimeric complexes between the four receptors leading to signal amplification and downstream activities. More than one third of glioblastoma cases show gene amplification of epidermal growth factor receptor (EGFR) which can be in truncated or rearranged form. The eTag assay system (Monogram) is an antibody based fluorescent assay that has the potential to assess the activation state of the EGFR signaling pathway. Methods: Twenty three cases of glioblastoma were selected for eTag analysis. There were twelve males and eleven females with ages ranging from 20–84 years. After reviewing the histology, 10 micron sections were cut from formalin fixed paraffin embedded (FFPE) tumor tissue blocks. Specific monoclonal antibodies of the Erb family bound to a fluorescent reporter (eTag) were applied to tissue sections. After binding of specific analyte, a second monoclonal antibody is added which acts as molecular scissors resulting in cleavage of “eTags”. The released eTag molecules are separated by capillary electrophoresis and measured as relative fluorescent units. Various FFPE tumor cell lines were used as controls. Results: Nineteen out of twenty three tumors (82%) showed the presence of dimers of the Erb family signaling pathway. High levels of intra and /or extracellular EGFR homodimers (HER-1-HER-1) were detected in eight samples (35%). EGFR-HER-3 dimers and EGFR-HER-2 dimers were seen at high levels in four and six samples (17% and 26% respectively). High levels of HER-2-HER3 dimers were detected in six samples (26%). Conclusion: The EGFR signaling pathway plays a substantial role in tumorigenesis of glioblastoma. Identification of receptor homo and heterodimers may be of value during treatment planning of individual patients. No significant financial relationships to disclose.

scholarly journals KIF15 Promotes Progression of Castration Resistant Prostate Cancer by Activating EGFR Signaling Pathway

2021 ◽  
Vol 11 ◽  
Author(s):  
Lin Gao ◽  
Ru Zhao ◽  
Junmei Liu ◽  
Wenbo Zhang ◽  
Feifei Sun ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Signaling Pathway ◽  
Growth Factor Receptor ◽  
Clinical Problem ◽  
Mitogen Activated Protein Kinase ◽  
Dependent Manner ◽  
Castration Resistant Prostate Cancer ◽  
Egfr Signaling ◽  
Castration Resistant ◽  
Egfr Signaling Pathway

Castration-resistant prostate cancer (CRPC) continues to be a major clinical problem and its underlying mechanisms are still not fully understood. The epidermal growth factor receptor (EGFR) activation is an important event that regulates mitogenic signaling. EGFR signaling plays an important role in the transition from androgen dependence to castration-resistant state in prostate cancer (PCa). Kinesin family member 15 (KIF15) has been suggested to be overexpressed in multiple malignancies. Here, we demonstrate that KIF15 expression is elevated in CRPC. We show that KIF15 contributes to CRPC progression by enhancing the EGFR signaling pathway, which includes complex network intermediates such as mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)/AKT pathways. In CRPC tumors, increased expression of KIF15 is positively correlated with EGFR protein level. KIF15 binds to EGFR, and prevents EGFR proteins from degradation in a Cdc42-dependent manner. These findings highlight the key role of KIF15 in the development of CRPC and rationalize KIF15 as a potential therapeutic target.

Single Nucleotide Polymorphisms in MicroRNA-Binding Site of Epidermal Growth Factor Receptor Signaling Pathway and Susceptibility to Esophageal Squamous Cell Carcinoma

2019 ◽  
Vol 38 (1) ◽  
pp. 1-8 ◽  
Author(s):  
Yanhong Qu ◽  
Yougai Zhang ◽  
Kaijuan Wang ◽  
Chunhua Song ◽  
Peng Wang ◽  
...  
Keyword(s):  
Binding Site ◽  
Signaling Pathway ◽  
Target Genes ◽  
Growth Factor Receptor ◽  
Nucleotide Polymorphisms ◽  
Egfr Signaling ◽  
Single Nucleotide ◽  
Egfr Signaling Pathway ◽  
Gene Environment ◽  
Epidermal Growth

Background: Epidermal growth factor receptor (EGFR) signaling pathway plays a fundamental role in regulating cell proliferation, differentiation, apoptosis, migration, and so on, which are associated with tumor development, including the esophageal squamous cell carcinoma (ESCC). The single nucleotide polymorphisms (SNPs) of microRNA-binding sites with target genes in the EGFR pathway could lead to alteration in the combination of microRNA with target genes and contribute to the susceptibility of cancer. Methods: A case-control study including 494 ESCC patients and 494 controls was carried out to investigate the genetic susceptibility of 4 microRNA-binding site SNPs (rs712 in the binding site of KRAS to let-7, rs8904 in the binding site of NFBIA to mir-507, rs3738894 in the binding site of protein kinase C epsilon to mir-218, rs701848 in the binding site of phosphatase and tensin to mir-1304) as well as the interactions of gene-environment in the development of ESCC. Results: The results showed that compared with CC genotype, the individuals with TT and TT + CT genotypes of rs701848 were significantly associated with increased ESCC risk (OR adjusted 1.56, 95% CI 1.07–2.27 and 1.41, 1.01–1.97). The gene-Environment interaction between rs3738894 and smoking history was associated with the risk of esophageal cancer. Conclusions: Results of these analyses underline the support of the notion that SNPs in microRNA-binding site of EGFR signaling pathway play certain important roles in the susceptibility to ESCC.

scholarly journals Quercetin Attenuates Podocyte Apoptosis of Diabetic Nephropathy Through Targeting EGFR Signaling

2022 ◽  
Vol 12 ◽  
Author(s):  
Yiqi Liu ◽  
Yuan Li ◽  
Liu Xu ◽  
Jiasen Shi ◽  
Xiujuan Yu ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Signaling Pathway ◽  
Growth Factor Receptor ◽  
Network Pharmacology ◽  
Egfr Signaling ◽  
Egfr Signaling Pathway ◽  
Novel Approach ◽  
Apoptotic Protein ◽  
Epidermal Growth

Podocytes injury is one of the leading causes of proteinuria in patients with diabetic nephropathy (DN), and is accompanied by podocytes apoptosis and the reduction of podocyte markers such as synaptopodin and nephrin. Therefore, attenuation of podocyte apoptosis is considered as an effective strategy to prevent the proteinuria in DN. In this study, we evaluated the anti-podocyte-apoptosis effect of quercetin which is a flavonol compound possessing an important role in prevention and treatment of DN and verified the effect by using db/db mice and high glucose (HG)-induced mouse podocytes (MPs). The results show that administration of quercetin attenuated the level of podocyte apoptosis by decreasing the expression of pro-apoptotic protein Bax, cleaved caspase 3 and increasing the expression of anti-apoptotic protein Bcl-2 in the db/db mice and HG-induced MPs. Furthermore, epidermal growth factor receptor (EGFR) was predicted to be the potential physiological target of quercetin by network pharmacology. In vitro and vivo experiments confirmed that quercetin inhibited activation of the EGFR signaling pathway by decreasing phosphorylation of EGFR and ERK1/2. Taken together, this study demonstrates that quercetin attenuated podocyte apoptosis through inhibiting EGFR signaling pathway, which provided a novel approach for further research of the mechanism of quercetin in the treatment of DN.

A multiplex technology platform for the rapid detection of relevant mutations in the EGFR signaling pathway.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 386-386
Author(s):  
E. Labourier ◽  
D. Smith ◽  
W. Laosinchai-Wolf ◽  
L. Friar ◽  
J. Houghton ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Cell Lines ◽  
Braf V600e ◽  
Analytical Sensitivity ◽  
Egfr Signaling ◽  
Kras Mutations ◽  
Technology Platform ◽  
Egfr Signaling Pathway ◽  
Cancer Types ◽  
Exon 19

386 Background: Determination of the mutational status of key gene effectors along the EGFR signaling pathway plays a critical role in the management of metastatic colorectal cancer (mCRC) and other cancer types. We previously reported the rapid, multiplex, and sensitive detection of 7 common KRAS mutations in mCRC FFPE specimens using the Signature KRAS Mutations (RUO) kit. We show here that the same technology platform can be applied to the detection of additional clinically relevant mutations in the EGFR, BRAF, KRAS, NRAS and HRAS genes. Methods: Mutation panels were designed for multiplex PCR amplification of an internal control gene and discrete mutation regions in independent target genes. PCR products were hybridized on a liquid bead array carrying target-specific probes and sorted by flow cytometry using a Luminex 200 system. Genomic DNA was extracted from cell lines and representative flash frozen, FFPE or FNA clinical specimens using laboratory-validated extraction methods. Results: Using model plasmids and cell lines we developed specific assays for distinct mutations in KRAS codon 12/13, KRAS 3' UTR (rs61764370), BRAF codon 600/601, HRAS codon 12/61, NRAS codon 61, and EGFR exon 19/20/21. The various assays reached 0.1 to 5% analytical sensitivity and could be further combined in multiplex panels relevant to specific applications. The Signature KRAS/BRAF Mutations (RUO) kit, an assay for 12 KRAS mutations in codon 12/13 and BRAF V600E, was validated in over 250 mCRC FFPE specimens with >99% agreement with clinically validated methods. Specific detection of these 13 mutations and 6 HRAS/NRAS mutations was also demonstrated in thyroid nodule FNA specimens. Single-well detection of EGFR deletions in exon 19 together with the point mutations L858R and T790M was also successfully evaluated in lung specimens. Conclusions: The Signature technology platform is a specific, sensitive and flexible tool for the assessment of various mutations in different tissue types. The development and validation of broader mutation panels would likely facilitate the rapid molecular characterization of individual tumor specimens and the optimization of personalized treatments for mCRC and other cancer types. [Table: see text]

scholarly journals SAT-151 Regulation of Low-Density Lipoprotein Receptor Expression in Triple Negative Breast Cancer

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Tiffany Scully ◽  
Nathan G Kase ◽  
Emily Jane Gallagher ◽  
Derek LeRoith
Keyword(s):  
Breast Cancer ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Triple Negative ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Receptor ◽  
Egfr Signaling ◽  
Egfr Signaling Pathway ◽  
Density Lipoprotein Receptor

Abstract Preclinical models and clinical studies suggest that hypercholesterolemia promotes breast cancer progression 1,2. The expression of the low-density lipoprotein receptor (LDLR) has been positively associated with poorer recurrence-free survival in human breast cancer studies 3. Mechanistically, LDLR has been demonstrated to play a role in the increased tumor growth associated with hypercholesterolemia, as knock-down of LDLR led to decreased tumor growth in setting of elevated circulating LDL cholesterol. The aim of this study was to identify factors which up-regulate expression of LDLR in triple negative breast cancer (TNBC). In glioblastoma, hyper-activation of the epidermal growth factor receptor (EGFR) signaling pathway has been associated with greater LDLR expression and susceptibility to targeting of cholesterol metabolism4. As EGFR is frequently expressed in TNBC5, we examined if increased LDLR expression is associated with activation of the EGFR signaling pathway in TNBC. The expression of LDLR in the TNBC cell lines, MDA-MB-231 (231) and MDA-MB-468 (468) was examined pre- and post-EGF stimulation of the EGFR and in the presence of chemical inhibitors. Cells were grown in DMEM/10% FBS/1% Pen/strep (P/S), and experiments were performed under reduced serum conditions at 1.25%FBS/DMEM/1%P/S. In the absence of stimulation, LDLR protein expression was 3-fold higher in 231 vs 468 cell lines. This was despite mRNA expression being comparable at baseline, suggesting that the difference in protein expression was post-transcriptionally mediated. Treatment with 10 ng/mL EGF for 2 hours led to an increased activation of the EGFR, phosphorylation of Akt and extracellular signal regulated kinase (ERK) in both cell lines but induced an increase in LDLR protein and mRNA expression only in 468 cells. Treatment of 468 cells with EGF after exposure to actinomycin, a transcription inhibitor, revealed that EGF treatment resulted in reduced degradation of LDLR mRNA (p = 0.002) over 3 hours, suggesting that the EGF-induced increase in LDLR expression was by protection of LDLR mRNA from degradation. Chemical inhibition of the ERK pathway with 20 μM UO126 reduced both the EGF-induced increase in LDLR expression in 468 cells (p = 0.015) as well as the high baseline expression of LDLR by half in 231 cells (p = 0.001). Overall our results suggest that the EGFR/ERK signaling pathway regulates LDLR expression in TNBC, supporting the increased anabolic needs of this aggressive, swiftly expanding form of breast cancer. References: 1Alikhani, N. et al., Oncogene32, 961-967 (2013), 2Pelton, K. et al., Am. J. Pathol.184, 2099-2110 (2014), 3Gallagher, E. J. et al., Oncogene36, 6462-6471 (2017), 4Guo, D. et al., Cancer Discov.1, 442-456 (2011), 5Reis-Filho, J. S. & Tutt, A. N. J. Histopathology52, 108-118 (2008).

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