Differential gene expressions in dose-related radioresistant hypopharyngeal cancer cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE102594 | GEO | 2020/08/11
REPOSITORIES: GEO
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Project description:Through measuring expression levels of lncRNAs/mRNAs in RS-FaDu vs. FaDu cells at 0, 24 and 48 h after 4 Gy radiation, we identified a number of lncRNAs/mRNAs with dysregulation. And the microarray data were verified by qRT-PCR assays. By informatics analyses, we predicted pathways, which were potentially associated with radioresistance of hypopharyngeal carcinoma.
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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:It has been confirmed that nsun2 promotes cell proliferation and migration in hypopharyngeal cancer cell lines, but the pathway of nsun2 in hypopharyngeal cancer cell lines is poorly understood. We constructed stable cell lines by knocking down nsun2 to find the key genes of downstream pathway, and compared them with normal FaDu cell lines.It has been confirmed that nsun2 promotes cell proliferation and migration in FaDu cell line, but the pathway of nsun2 in FaDu cell line is poorly understood. We constructed stable cell lines by knocking down nsun2 to find the key genes of downstream pathway, compared them with normal FaDu cell lines.
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Project description:Prostate cancer cell lines DU145 and LNCaP were purchased from the American Type Culture Collection. Radioresistant (RR) sublines were generated form these original parental radiosensitive (RS) cell lines. Gene expression profiles of radiosensitive (RS) and radioresistant (RR) prostate cancer cell lines were measured.
2019-10-11 | GSE134499 | GEO
Project description:Prostate cancer cell lines DU145 and LNCaP were purchased from the American Type Culture Collection. Radioresistant (RR) sublines were generated form these original parental radiosensitive (RS) cell lines. aCGH profiles of radiosensitive (RS) and radioresistant (RR) prostate cancer cell lines were measured and compared to normal DNA.
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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: Research using in vitro canine mammary carcinoma cell lines and studies involving naturally occurring canine mammary tumours are not only fundamental models used to advance the understanding of cancer in veterinary patients but are also regarded as excellent translational models for human breast cancer. In human medicine, following disease classification and staging breast cancer is typically treated with multimodal therapies including radiotherapy. 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. Comparative canine and human studies investigating the molecular mechanisms of radioresistance may lead to the development of effective cancer treatments that benefit both species. Methods: Human (MDA-MB-231, MCF-7 and ZR-751) and canine (REM-134) radioresistant cell lines were established by exposing 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 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. Results: Colony formation assays identified a range of intrinsic radiosensitivities in the human and canine parental cell lines with the REM-134 cell line showing significantly greater radioresistance compared to the human cell lines. Colony formation and proliferation assays confirmed radioresistance in all developed radioresistant cell lines. Radioresistant cells exhibited enhanced migration and invasion, with evidence of epithelial-to-mesenchymal-transition. Gene analysis identified that following the acquisition of radioresistance in MCF-7 and ZR-751 cell lines the cell lines 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. MDA-MB-231 and MDA-MB-231 RR cell lines both classified as basal, whereas the REM-134 and REM-134 RR cell lines with enriched for HER2 overexpression. 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: To our knowledge, our study is the first to develop a canine radioresistant cell line and provide a comparative genetic and phenotypic analysis of the mechanisms of acquired radioresistance between canine and human cell lines. The cellular process that occur with the development of acquired radioresistance are similar between the human and canine cell lines; this suggests that not only is the canine model an appropriate model to study human disease but that treatment strategies used in human medicine may also be applicable to veterinary patients.
2020-07-08 | GSE149988 | 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.
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