Global transcriptional profiling of HCC827 lung adenocarcinoma cells in response to EGFR inhibition
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA740291 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR14890346_1.fastq.gz | Fastqsanger.gz | |||
| SRR14890346_2.fastq.gz | Fastqsanger.gz | |||
| SRR14890347_1.fastq.gz | Fastqsanger.gz | |||
| SRR14890347_2.fastq.gz | Fastqsanger.gz | |||
| SRR14890348_1.fastq.gz | Fastqsanger.gz |
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Project description:mRNA sequencing of EGFR mutant HCC827 lung adenocarcinoma cells were treated with erlotinib (EGFR inhibitor) for 24hr to profile and characterize dysregulated pathways in response to EGFR inhibition
2021-06-24 | GSE178755 | GEO
Project description:Lung adenocarcinoma cells harboring epidermal growth factor receptor (EGFR) mutations are sensitive to EGFR tyrosine kinase inhibitors (TKIs). Prolonged cancer treatment will induce the development of acquired resistance to EGFR TKI. To gain insight into the molecular mechanisms of EGFR-TKIs resistance, we generate EGFR-TKI-resistant HCC827-8-1 cells to be analyzed by microarray with their parental HCC827cells. gefitinib resistant HCC827-8-1 cells with three replications; gefitinib-sensitive HCC827 cells with three replications
2016-08-23 | E-GEOD-74575 | biostudies-arrayexpress
Project description:EGFR mediates stabilities of a wide spectrum of proteins. Treatment of the cells with EGFR tyrosine kinase inhibitors (EGFR-TKIs) leads to degradation of these proteins. To define the proteins and corresponding pathways of EGFR-stabilized proteins, we use mass spectrum to quantify the protein levels in the untreated control HCC827 cells and the cells treated with erlotinib or gefitinib.
2025-05-13 | PXD050420 | Pride
Project description:Human EGFR-mutated lung adenocarcinoma cell lines HCC4006, HCC827 and PC9 were treated with trametinib or DMSO to assess the impact on transcription.
2021-07-19 | E-MTAB-9889 | biostudies-arrayexpress
Project description:Lung adenocarcinoma cells harboring epidermal growth factor receptor (EGFR) mutations are sensitive to EGFR tyrosine kinase inhibitors (TKIs). Prolonged cancer treatment will induce the development of acquired resistance to EGFR TKI. To gain insight into the molecular mechanisms of EGFR-TKIs resistance, we generate EGFR-TKI-resistant HCC827-8-1 cells to be analyzed by microarray with their parental HCC827cells.
2016-08-23 | GSE74575 | GEO
Project description:The model is based on publication:
Mathematical analysis of gefitinib resistance of lung adenocarcinoma caused by MET amplification
Abstract:
Gefitinib, one of the tyrosine kinase inhibitors of epidermal growth factor receptor (EGFR), is effective for treating lung adenocarcinoma harboring EGFR mutation; but later, most cases acquire a resistance to gefitinib. One of the mechanisms conferring gefitinib resistance to lung adenocarcinoma is the amplification of the MET gene, which is observed in 5–22% of gefitinib-resistant tumors. A previous study suggested that MET amplification could cause gefitinib resistance by driving ErbB3-dependent activation of the PI3K pathway. In this study, we built a mathematical model of gefitinib resistance caused by MET amplification using lung adenocarcinoma HCC827-GR (gefitinib resistant) cells. The molecular reactions involved in gefitinib resistance consisted of dimerization and phosphorylation of three molecules, EGFR, ErbB3, and MET were described by a series of ordinary differential equations. To perform a computer simulation, we quantified each molecule on the cell surface using flow cytometry and estimated unknown parameters by dimensional analysis. Our simulation showed that the number of active ErbB3 molecules is around a hundred-fold smaller than that of active MET molecules. Limited contribution of ErbB3 in gefitinib resistance by MET amplification is also demonstrated using HCC827-GR cells in culture experiments. Our mathematical model provides a quantitative understanding of the molecular reactions underlying drug resistance.
2024-09-02 | BIOMD0000000827 | BioModels
Project description:The receptor tyrosine kinase (RTK) EGFR is overexpressed and mutated in NSCLC. These mutations can be targeted by RTK inhibitors (TKIs), such as erlotinib. Chromatin-modifying agents offer a novel therapy approach by sensitizing tumor cells to TKIs. The NSCLC cell lines HCC827 (EGFR mutant, adenocarcinoma), A549 (EGFR wt, adenocarcinoma) and NCI-H460 (EGFR wt, large cell carcinoma) were analyzed by SNP6.0 array. Changes in proliferation were quantified by WST-1 assay, apoptosis by Annexin V/7-AAD flow cytometry and histone marks (acH3, H3K4me1,-2,-3) by immunoblotting. Expectedly, the EGFR wt cell lines A549 and NCI-H460 were insensitive to the growth-inhibiting effect of single-agent erlotinib (IC50 70-100µM), compared to HCC827 (IC50 <0.02μM). Treatment with panobinostat diminished growth to <50% in both EGFR wt and <30% in HCC827 cells. The combination of both drugs significantly reduced proliferation by ≥70% in A549, >95% in HCC827, but not further in NCI-H460. Panobinostat alone induced differentiation and expression of p21WAF1/CIP1 and p53 in all three cell lines, with almost no further increase when combined with erlotinib. In contrast, combination treatment additively decreased pERK, pAKT and pEGFR in A549, and synergistically induced acH3 in both adenocarcinoma lines. Surprisingly, we also saw an induction of H3K4 methylation marks in all three cell lines. In conclusion, panobinostat synergistically sensitized lung adenocarcinoma cells to the antiproliferative effects of erlotinib. Since single-agent erlotinib has only modest clinical effects in adenocarcinoma EGFR wt patients, combination therapy with an HDACi might offer a promising therapy approach to extend this activity. Copy-number analysis of three NSCLC cell lines HCC827, A549 and NCI-H460 (in unicates) was performed according to protocol by Affymetrix Genome-Wide Human SNP-Array 6.0.
2014-12-03 | E-GEOD-63784 | biostudies-arrayexpress
Project description:Background: The receptor tyrosine kinase (RTK) EGFR is overexpressed and mutated in NSCLC. These mutations can be targeted by RTK inhibitors (TKIs) such as erlotinib. Chromatin-modifying agents may offer a novel therapeutic approach by sensitizing tumor cells to TKIs. Methods: The NSCLC cell lines HCC827 (EGFR mutant, adenocarcinoma), A549 (EGFR wt, adenocarcinoma) andNCI-H460 (EGFR wt, large cell carcinoma) were analyzed by SNP6.0 array. Changes in proliferation after panobinostat (LBH-589, PS) and erlotinib treatment were quantified by WST-1 assay and apoptosis by Annexin V/7-AAD flow cytometry. Abundance of target proteins and histone marks (acH3, H3K4me1/2/3) was determined by immunoblotting. Results: As expected, the EGFR wt cell lines A549 and NCI-H460 were quite insensitive to the growth-inhibitory effect of single-agent erlotinib (IC50 70-100 μM), compared to HCC827 (IC50 < 0.02 μM). PS treatment diminished growth to <50 % in both EGFR wt cells, and <30 % in HCC827. The combination of both drugs reduced proliferation by >95 % in HCC827, ≥70 % in A549, but not further in NCI-H460. PS alone induced differentiation and expression of p21WAF1/CIP1 and p53 and decreased CHK1 in all three cell lines, with almost no further effect when combined with erlotinib. In contrast, combination treatment additively decreased pEGFR, pERK, pAKT in A549, and synergistically induced acH3 in both adenocarcinoma lines. Surprisingly, we saw an induction of H3K4 methylation marks after erlotinib treatment in HCC827 (and to a lesser extent in A549) that was even further enhanced by combination with PS. Conclusion: We were able to show that PS synergistically sensitized lung adenocarcinoma cells to the antiproliferative effects of erlotinib. Since single-agent erlotinib has only modest clinical effects in lung adenocarcinoma EGFR wt patients, its combination with an HDACi might offer a promising therapy approach.
2014-12-03 | GSE63784 | GEO
Project description:Purpose: Multiple mechanims have been proposed that lead to reduced effectiveness of EGFR tyrosine kinase inhibitors (TKIs) in lung cancer and yet resistance to osimertinib and gefitinib still remains a challenge in the clinic. The goals of this study are to identify key genes contributing to tolerance and resistance to EGFR inhibition. Methods: mRNA profiles of gefitinib and osimertinib tolerant cells in PC9 and HCC827 cells were generated by deep sequencing using Illumina. In addition, mRNA profiles of cells (AALE, PC9 and HCC827) overexpressing with miR-147b or miR-21 and mRNA profiles of cells (H1975 and PC9ER) with miR-147b and miR-21 knocking down were generated by deep sequencing. The mappable reads were aligned to the human transcripts using Bowtie2 and gene abundance was estimated using RSEM. Results: Upregulation of miR-147b and miR-21 expression is related to tolerance and resistance to gefitinib and osimertinib in lung cancer. The signaling pathways of transcripts by knocking down miR-147b or miR-21 in resistant cells (H1975 and PC9ER) and by overexpressing miR-147b or miR-21 in both sensistive cells (HCC827 and PC9) and immortalized lung epithelial cells (AALE) are consistent with the key signaling pathways shown in tolerant cells to gefitinib and osimertinib in HCC827 and PC9 cells (HCC827GTR/OTR vs HCC827 and PC9GTR/OTR vs PC9). Conclusions: Our work identifies key signaling pathways that mediate EGFR-TKI tolerance and resistance in lung cancer. Our study provides potential targets to improve the efficacy of EGFR-TKIs therapy in cancer pagtients.
2018-01-11 | GSE103350 | GEO
Project description:EGFR tyrosine kinase inhibitors (TKIs) have demonstrated tremendous clinical benefits in non-small cell lung cancer (NSCLC) patients. However, resistance emerges rapidly due to a variety of mechanisms including a secondary mutation of T790M in EGFR that abrogates the binding of the drugs. It has been postulated that EGFR TKIs, such as afatinib (BIBW2992), with activity against the T790M mutant EGFR kinase might overcome the drug resistance problem or, when used as the first-line treatment, delay or suppress the emergence of resistance in EGFR. In this study, we generated BIBW2992-resistant cells, HCC827-BR1 and HCC827-BR2, from the parental HCC827 cells. In HCC827-BR cells, EGFR, MET, and Erb2 were down-regulated and no secondary mutation was found to be present in the coding region of EGFR. Gene set enrichment analysis (GSEA) revealed an obvious signature of epithelial to mesenchymal transition (EMT) in the drug resistant cells. Subsequently, the HCC827-BR cells were shown to be more invasive. Most importantly, we strived to seek if alternative medicine might be applied alone or in combination to treat the BIBW2992-resistant cells or to, under BIBW2992 treatment, diminish the emergence of resistant cells. Compared to the parental cells, the HCC827-BR cells were more sensitive to dasatinib, an FDA-approved kinase inhibitor. Furthermore, as revealed in the clonogenicity assay, the reduction of tumor-colony-forming cells after exposure to BIBW2992 was substantially potentiated by low concentration of dasatinib. Thus, prospective clinical investigations may be needed to evaluate if dasatinib can be beneficial to patients receiving second-generation EGFR TKIs for the treatment of NSCLC. Over a period of 3-4 months, BIBW2992-resistant cells were isolated in cell culture by maintenance of HCC827 cells in the presence of escalating concentrations of BIBW2992 up to 2 μM. Two cell lines, HCC827-BR1 and HCC827-BR2, were established based on individual clones. Total RNA of these HCC827, HCC827-BR1 and HCC827-BR2, were extracted for gene expression microarray analysis using Illumina HumanHT12 v3 BeadChip.
2016-10-22 | E-GEOD-62504 | biostudies-arrayexpress