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Microarray data analysis reveals gene expression changes in response to ionizing radiation in MCF7 human breast cancer cells.

ABSTRACT: BACKGROUND:The aim of this study was to identify potential therapeutic target genes for breast cancer (BC) by the investigation of gene expression changes after ionizing radiation (IR) in BC cells. Gene expression profile GSE21748, including BC cell line MCF-7 samples at different time points after IR treatment, were downloaded from Gene Expression Omnibus. Differentially expressed genes (DEGs) were identified in different time points following IR compared with cell samples before IR, respectively. Gene ontology functions and The Kyoto Encyclopedia of Genes and Genomes pathways of the overlapping DEGs were enriched using DAVID. Transcription factor (TFs)-encoding genes were identified from the overlapping DEGs, followed by construction of transcriptional regulatory network and co-expression network. RESULTS:A total of 864 overlapping DEGs were identified, which were significantly enriched in regulation of cell proliferation and apoptosis, and cell cycle process. We found that FOXD1, STAT6, XBP1, STAT2, LMO2, TFAP4, STAT3, STAT1 were hub nodes in the transcriptional regulatory network of the overlapping DEGs. The co-expression network of target genes regulated by STAT3, STAT1, STAT6 and STAT2 included some key genes such as BCL2L1. CONCLUSION:STAT1, STAT2, STAT3, STAT6, XBP1, BCL2L1, CYB5D2, ESCO2, and PARP2 were significantly affected by IR and they may be used as therapeutic gene targets in the treatment of BC.

SUBMITTER: Bai J

PROVIDER: S-EPMC7650302 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Microarray data analysis reveals gene expression changes in response to ionizing radiation in MCF7 human breast cancer cells.

Bai Jing J Luo Youzhen Y Zhang Shengchu S

Hereditas 20200903 1

<h4>Background</h4>The aim of this study was to identify potential therapeutic target genes for breast cancer (BC) by the investigation of gene expression changes after ionizing radiation (IR) in BC cells. Gene expression profile GSE21748, including BC cell line MCF-7 samples at different time points after IR treatment, were downloaded from Gene Expression Omnibus. Differentially expressed genes (DEGs) were identified in different time points following IR compared with cell samples before IR, re ...[more]

PMID: 32883354

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Project description:BackgroundBreast tissue is among the most sensitive tissues to the carcinogenic actions of ionizing radiation and epidemiological studies have linked radiation exposure to breast cancer. Currently, molecular understanding of radiation carcinogenesis in mammary gland is hindered due to the scarcity of in vivo long-term follow up data. We undertook this study to delineate radiation-induced persistent alterations in gene expression in mouse mammary glands 2-month after radiation exposure.MethodsSix to eight week old female C57BL/6J mice were exposed to 2 Gy of whole body ? radiation and mammary glands were surgically removed 2-month after radiation. RNA was isolated and microarray hybridization performed for gene expression analysis. Ingenuity Pathway Analysis (IPA) was used for biological interpretation of microarray data. Real time quantitative PCR was performed on selected genes to confirm the microarray data.ResultsCompared to untreated controls, the mRNA levels of a total of 737 genes were significantly (p<0.05) perturbed above 2-fold of control. More genes (493 genes; 67%) were upregulated than the number of downregulated genes (244 genes; 33%). Functional analysis of the upregulated genes mapped to cell proliferation and cancer related canonical pathways such as 'ERK/MAPK signaling', 'CDK5 signaling', and '14-3-3-mediated signaling'. We also observed upregulation of breast cancer related canonical pathways such as 'breast cancer regulation by Stathmin1', and 'HER-2 signaling in breast cancer' in IPA. Interestingly, the downregulated genes mapped to fewer canonical pathways involved in cell proliferation. We also observed that a number of genes with tumor suppressor function (GPRC5A, ELF1, NAB2, Sema4D, ACPP, MAP2, RUNX1) persistently remained downregulated in response to radiation exposure. Results from qRT-PCR on five selected differentially expressed genes confirmed microarray data. The PCR data on PPP4c, ELF1, MAPK12, PLCG1, and E2F6 showed similar trend in up and downregulation as has been observed with the microarray.ConclusionsExposure to a clinically relevant radiation dose led to long-term activation of mammary gland genes involved in proliferative and metabolic pathways, which are known to have roles in carcinogenesis. When considered along with downregulation of a number of tumor suppressor genes, our study has implications for breast cancer initiation and progression after therapeutic radiation exposure.

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Microarray data analysis reveals gene expression changes in response to ionizing radiation in MCF7 human breast cancer cells.

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Microarray data analysis reveals gene expression changes in response to ionizing radiation in MCF7 human breast cancer cells.

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