DNA damage repair gene expression profiles in cervical cancer cells radioresistant to 252Cf neutron and X-rays
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE19526 | GEO | 2009/12/17
SECONDARY ACCESSION(S): PRJNA122241
REPOSITORIES: GEO
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Project description:[original title] Microarray analysis of DNA damage repair gene expression profiles in cervical cancer cells radioresistant to 252Cf neutron and X-rays. The aim of the study was to obtain stable radioresistant sub-lines from the human cervical cancer cell line HeLa by prolonged exposure to 252Cf neutron and X-rays. Radioresistance mechanisms were investigated in the resulting cells using SuperArray Oligo GEArray® Human DNA Damage Signaling Pathway Microarray. HeLa cells were treated with fractionated 252Cf neutron and X-rays, with a cumulative dose of 75 Gy each, over 8 months, yielding the sub-lines HeLaNR and HeLaXR.Gene expression patterns of the radioresistant sub-lines were studied through microarray analysis
2010-05-17 | E-GEOD-19526 | biostudies-arrayexpress
Project description:To explore factors contributing to radioresistance in GBM, we established GBM radioresistant cell line using U87MG human GBM cells.
2022-06-29 | GSE207002 | GEO
Project description:To explore elements contributing to radioresistance in breast cancer, we established radioresistant human breast cancer cell line MCF-7.
2022-08-06 | GSE210411 | GEO
Project description:Background: Radiotherapy plays an important role in the multimodal treatment of breast cancer. The response of a breast tumour to radiation depends not only on its innate radiosensitivity but also on tumour repopulation by cells that have developed radioresistance. Development of effective cancer treatments will require further molecular dissection of the processes that contribute to resistance. Methods: Radioresistant cell lines were established by exposing MDA-MB-231, MCF-7 and ZR-751 parental cells to increasing weekly doses of radiation. The development of radioresistance was evaluated through proliferation and colony formation assays. Phenotypic characterisation included migration and invasion assays and immunohistochemistry. Intrinsic differences and changes in response to radiation between parental and radioresistant cells were investigated by whole-transcriptome gene expression analysis. Gene enrichment and pathway-focused analyses identified signalling networks differentially activated in radioresistant cells, which were confirmed by western blotting. Results: Proliferation and colony formation assays confirmed radioresistance. Radioresistant cells exhibited enhanced migration and invasion, with evidence of epithelial-to-mesenchymal-transition, and limited activation of DNA damage and apoptotic pathways in response to 2 Gy ionising radiation. Significantly, acquisition of radioresistance in MCF-7 and ZR-751 cell lines resulted in a loss of expression of both ERα and PgR and an increase in EGFR expression; based on gene analysis they changed subtype classification from their parental luminal A to HER2-overexpressing (MCF-7 RR) and normal-like (ZR-751 RR) subtypes, indicating the extent of phenotypic changes and cellular plasticity involved in this process. Whole-transcriptome gene expression analysis identified down-regulation of ER signalling genes and up-regulation of genes associated with PI3K, MAPK and WNT pathway activity in radioresistant cell lines derived from ER+ cells; this was confirmed by western blot, which showed increased p-AKT and p-ERK expression following radiation. Conclusions: This is the first study to date that extensively describes the development and characterisation of three novel radioresistant breast cancer cell lines through both genetic and phenotypic analysis. More changes were identified between parental cells and their radioresistant derivatives in the ER+ (MCF-7 and ZR-751) compared with the ER- cell line (MDA-MB-231) model; however, multiple and likely interrelated mechanisms were identified that may contribute to the development of acquired resistance to radiotherapy.
2018-10-04 | GSE120798 | GEO
Project description:The clinical management of locally advanced oesophageal adenocarcinoma (OAC) commonly involves neoadjuvant chemoradiotherapy (CRT), but complete pathological response to CRT only occurs in 20-30% of patients, as radioresistance remains a major clinical challenge. In this study we used an established isogenic cell line model of radioresistant OAC to detect proteomic signatures of radioresistance in order to identify novel potential molecular and cellular targets of radioresistance in OAC. Intracellular proteins obtained from radiosensitive (OE33P) and radioresistant (OE33R) cells were subjected to LC-MS/MS analysis. We identified 5785 proteins of which 251 were significantly modulated in OE33R cells, when compared to OE33P. Gene ontology and pathway analysis of the significantly modulated proteins demonstrated altered metabolism in radioresistant cells accompanied by an inhibition of apoptosis in OE33R cells. In addition, radioresistant cells were predicted to have an activation of inflammatory and angiogenic pathways when compared to the radiosensitive cells. For the first time, we performed a comprehensive proteomic profiling of our established isogenic cell line model of radioresistant OAC, providing insights into the molecular and cellular pathways which regulates radioresistance in OAC, and we provided pathway specific signatures of radioresistance that will aid further studies on the development of targeted therapies and personalised approaches to radiotherapy, with the ultimate goal of improving response to radiotherapy in cancer patients.
2022-08-18 | PXD020303 | Pride
Project description:Background: In the event of an improvised nuclear device detonation, the prompt radiation exposure would consist of γ rays plus a neutron component that would contribute to the total dose. As neutrons cause more complex and difficult to repair damage to cells that would result in more severe health burden to affected individuals, it is paramount to be able to estimate the contribution of neutrons to an estimated dose, to provide information for those making treatment decisions. Results: Mice exposed to either 0.25 or 1 Gy of neutron or 1 or 4 Gy x-ray radiation were sacrificed at 1 or 7 days after exposure. Whole genome microarray analysis identified 7,285 and 5,045 differentially expressed genes in the blood of mice exposed to neutron or x-ray radiation, respectively. Neutron exposure resulted in mostly downregulated genes, whereas x-rays showed both down- and up-regulated genes. A total of 34 differentially expressed genes were regulated in response to all ≥1 Gy exposures at both times. Of these, 25 genes were consistently downregulated at days 1 and 7, whereas 9 genes, including the transcription factor E2f2, showed bi-directional regulation; being downregulated at day 1, while upregulated at day 7. Gene ontology analysis revealed that genes involved in nucleic acid metabolism processes were persistently downregulated in neutron irradiated mice, whereas genes involved in lipid metabolism were upregulated in x-ray irradiated animals. Most biological processes significantly enriched at both timepoints were consistently represented by either under- or over-expressed genes. In contrast, cell cycle processes were significant among down-regulated genes at day 1, but among up-regulated genes at day 7 after exposure to either neutron or x-rays. Cell cycle genes downregulated at day 1 were mostly distinct from the cell cycle genes upregulated at day 7. However, five cell cycle genes, Fzr1, Ube2c, Ccna2, Nusap1, and Cdc25b, were both downregulated at day 1 and upregulated at day 7. Conclusions: We describe, for the first time, the gene expression profile of mouse blood cells following exposure to neutrons. We have found that neutron radiation results in both distinct and common gene expression patterns compared with x-ray radiation.
2017-02-01 | GSE85323 | GEO
Project description:DNA damage repair gene expression profiles in cervical cancer cells radioresistant to 252Cf neutron and X-rays
| PRJNA122241 | ENA
Project description:In the current global scenario there is always a possibility that a terrorist group might acquire material to produce a nuclear device. In the likelihood of a detonation of an improvised nuclear device (IND) the prompt radiation would consist of both photons (gamma rays) and neutrons. As neutrons generally have a high Relative Biological Effectiveness (RBE) for most physiological endpoints, it is important to understand the impact that neutrons would have on the biodosimetry methods that are being developed for medical triage purposes. We have previously reported transcriptomic response in human and mouse blood to neutron exposure and determined its RBE compared to photons for gene induction. In this report, we studied the effect of mixed neutron-photon radiation on gene expression in human peripheral blood in order to mimic an IND type radiation observed increase in number as well as expression level of genes with increasing percentage of neutron in mixed exposures which peaked at 25% neutron exposure which was maximum neutron percentage used for the study. We identified 156 genes that responded significantly to all the neutron-photon mixed exposures. These genes were found to be mainly involved in p53 signaling and DNA damage response. The 25% neutron exposure also showed maximum enrichment of known neutron associated gene ontology terms reported in the previous studies. Analysis of upstream regulators of gene expression showed strong activation of TP53, SLC29A1, PDCD1 and suppression of ANLN, AURK and ANXA2 across all exposures. While AGT was exclusively activated by neutron specific exposures. We confirmed the expression of genes which showed increased expression as a function of increased neutron percentage using quantitative real-time RT-PCR which matched with the microarray data. Thus, the data in this current study clearly indicates that gene expression can be used to estimate the percentage of the neutron component in mixed neutron-photon exposures.
2020-09-02 | GSE113611 | GEO
Project description:Radiotherapy benefits more than 50% of cancer patients and cures 40% of them, where ionizing radiation deposits energy to cells and tissues, thereby eliciting DNA damage and resulting in cell death. Small GTPases are a superfamily of proteins that play critical roles in cell signaling. Several small GTPases, including RAC1, RHOB and RALA, were previously shown to modulate radioresistance in cancer cells. However, there is no systematic proteomic study on small GTPases that regulate radioresistance in cancer cells. Herein, we applied a high-throughput scheduled multiple-reaction monitoring (MRM) method, along with the use of synthetic stable isotope-labeled peptides, to identify differentially expressed small GTPase proteins in two pairs of breast cancer cell lines, MDA-MB-231 and MCF7, and their corresponding radioresistant lines. We identified 7 commonly altered small GTPase proteins with over 1.5-fold change in the two pairs of cell lines. We also discovered ARFRP1 as a novel radioresistance regulator, where its downregulation promotes radioresistance in breast cancer cells. Together, this represents the first comprehensive assessment about the differential expression of the small GTPase proteome associated with the development of radioresistance in breast cancer cells. Our work also uncovered ARFRP1 as a new target for enhancing radiation sensitivity in breast cancer.
2024-01-26 | PXD034360 | Pride
Project description:Most of the NPC patients suffer from local recurrences and distant metastases within 1.5 years after radiotherapy due to radioresistance. Distinct patterns of gene expression and signatures were found in NPC, and have been used to associate them with cell proliferation, apoptosis, invasion and metastasis, but few gene expression profiling studies have been focused on the tumor radioresistance.We used gene expression microarray analyses to identify the difference of mRNA in radioresistant NPC CNE2-IR cells and radiosensitive CNE2 cells. Radioresistant subclone of nasopharyngeal carcinoma CNE2-IR cell line was cultured and produced according to the experienment schedule to undergo five rounds of sublethal dose of irradiation (11 Gy), and the parent cell line CNE2 cell line sensitive to radiotherapy as the control
2013-12-10 | E-GEOD-48501 | biostudies-arrayexpress