Microarray analysis of genes associated with cell surface NIS protein levels in breast cancer
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Jhiang Sissy
PROVIDER: S-ECPF-GEOD-32161 | biostudies-other |
REPOSITORIES: biostudies-other
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Project description:BACKGROUND: Na+/I- symporter (NIS)-mediated iodide uptake allows radioiodine therapy for thyroid cancer. NIS is also expressed in breast tumors, raising potential for radionuclide therapy of breast cancer. However, NIS expression in most breast cancers is low and may not be sufficient for radionuclide therapy. We aimed to identify biomarkers associated with NIS expression such that mechanisms underlying NIS modulation in human breast tumors may be elucidated. METHODS: Published oligonucleotide microarray data within the National Center for Biotechnology Information Gene Expression Omnibus database were analyzed to identify gene expression tightly correlated with NIS mRNA level among human breast tumors. NIS immunostaining was performed in a tissue microarray composed of 28 human breast tumors which had corresponding oligonucleotide microarray data available for each tumor such that gene expression associated with cell surface NIS protein level could be identified. RESULTS AND DISCUSSION: NIS mRNA levels do not vary among breast tumors or when compared to normal breast tissues when detected by Affymetrix oligonucleotide microarray platforms. Cell surface NIS protein levels are much more variable than their corresponding NIS mRNA levels. Despite a limited number of breast tumors examined, our analysis identified cysteinyl-tRNA synthetase as a biomarker that is highly associated with cell surface NIS protein levels in the ER-positive breast cancer subtype. CONCLUSIONS: Further investigation on genes associated with cell surface NIS protein levels within each breast cancer molecular subtype may lead to novel targets for selectively increasing NIS expression/function in a subset of breast cancers patients.
| S-EPMC3205061 | biostudies-literature
Project description:Na+/I- symporter (NIS)-mediated iodide uptake allows radioiodine therapy for thyroid cancer. NIS is also expressed in breast tumors, raising potential for radionuclide therapy of breast cancer. However, NIS expression in most breast cancers is low and may not be sufficient for radionuclide therapy. A better understanding of the mechanisms of NIS regulation in breast cancer may lead to strategies for increasing cell surface NIS and radioactive iodide uptake (RAIU) in breast cancer. The MCF-7 cell line is the only human breast cancer cell line with inducible endogenous NIS expression. Kogai et al. [2000] first reported that trans-retinoic acid (tRA) induces NIS mRNA expression in MCF-7 cells and it was later reported that a combination treatment of tRA and hydrocortisone (tRA/H) further increases tRA-induced NIS expression/function in MCF-7 cells (Kogai et al., 2005; Dohan et al., 2006). In this study, we used gene expression profiling to identify genes that correlate with NIS expression in MCF-7 cells such that mechanisms underlying NIS modulation may be elucidated.
2011-09-16 | GSE32161 | GEO
Project description:Na+/I- symporter (NIS)-mediated iodide uptake allows radioiodine therapy for thyroid cancer. NIS is also expressed in breast tumors, raising potential for radionuclide therapy of breast cancer. However, NIS expression in most breast cancers is low and may not be sufficient for radionuclide therapy. A better understanding of the mechanisms of NIS regulation in breast cancer may lead to strategies for increasing cell surface NIS and radioactive iodide uptake (RAIU) in breast cancer. The MCF-7 cell line is the only human breast cancer cell line with inducible endogenous NIS expression. Kogai et al. [2000] first reported that trans-retinoic acid (tRA) induces NIS mRNA expression in MCF-7 cells and it was later reported that a combination treatment of tRA and hydrocortisone (tRA/H) further increases tRA-induced NIS expression/function in MCF-7 cells (Kogai et al., 2005; Dohan et al., 2006). In this study, we used gene expression profiling to identify genes that correlate with NIS expression in MCF-7 cells such that mechanisms underlying NIS modulation may be elucidated. MCF-7 cells were treated with DMSO vehicle, tRA (1µM), or tRA(1µM)/H(1µM) for 12 hours and total RNA was extracted. There are two replicates for each treatment group.
2011-09-15 | E-GEOD-32161 | biostudies-arrayexpress
Project description:ObjectiveThe aim of this study was to reveal the exact changes during the occurrence of breast cancer to explore significant new and promising genes or factors related to this disease.MethodsWe compared the gene expression profiles of breast cancer tissues with its uninvolved normal breast tissues as controls using the cDNA microarray analysis in seven breast cancer patients. Further, one representative gene, named IFI30, was quantitatively analyzed by real-time PCR to confirm the result of the cDNA microarray analysis.ResultsA total of 427 genes were identified with significantly differential expression, 221 genes were up-regulated and 206 genes were down-regulated. And the result of cDNA microarray analysis was validated by detection of IFI30 mRNA level changes by real-time PCR. Genes for cell proliferation, cell cycle, cell division, mitosis, apoptosis, and immune response were enriched in the up-regulated genes, while genes for cell adhesion, proteolysis, and transport were significantly enriched in the down-regulated genes in breast cancer tissues compared with normal breast tissues by a gene ontology analysis.ConclusionOur present study revealed a range of differentially expressed genes between breast cancer tissues and normal breast tissues, and provide candidate genes for further study focusing on the pathogenesis and new biomarkers for breast cancer.
| S-EPMC5643563 | biostudies-literature
Project description:We performed a microarray analysis to compare the expression profile of azurin treated and untreated with different P-cadherin expression levels. We also compared the differentially expressed genes regulated by P-cadherin overexpression. Both cell lines presented an up-regulation of apoptosis mediated by p53 protein, endocytosis and vesicle-mediated transport. Conversely, invasive MCF-7/AZ.Pcad cells treated with azurin presented a decreased expression of genes associated with cell surface receptors and signal transduction, as well as genes associated with biological adhesion and migration. Azurin is a bacterial protein from Pseudomonas aeruginosa which exerts an inhibitory activity in cancer cells. In P-cadherin-overexpressing models, a bad prognosis marker in breast cancer increasing invasion and other malignant features, azurin decreases the invasion of cancer cells. We performed a microarray analysis to compare the expression profile of azurin treated cells with different P-cadherin expression levels. Azurin up-regulated apoptosis mediated by p53 protein, endocytosis and vesicle-mediated transport. In the contrary, in invasive MCF-7/AZ.Pcad cells, azurin decreased the expression of genes associated with cell surface receptors and signal transduction, as well as biological adhesion. Further, azurin decreased adhesion of cells to proteins from the Extracellular matrix (ECM) and altered protein expression of integrins α6, β4 and β1 and interfered with the ability of these cells to form mammospheres. Altogether, our results further enlighten the anti-cancer effects mediated by azurin in P-cadherin overexpression breast cancer models. Cells were exposed to azurin (100uM) for 48h, after which total RNA was extracted. Control cells were exposed during the same time to PBS buffer solution. Three independent samples for each condition were used treated with different azurin production batches.
| S-ECPF-GEOD-54319 | biostudies-other
Project description:Cervical cancer is the second most commonly diagnosed type of cancer and the third leading cause of cancer-associated mortality in women. The current study aimed to determine the genes associated with cervical cancer development. Microarray data (GSE55940 and GSE46306) were downloaded from Gene Expression Omnibus. Overlapping genes between the differentially expressed genes (DEGs) in GSE55940 (identified by Limma package) and the differentially methylated genes were screened. Gene Ontology (GO) enrichment analysis was subsequently performed for these genes using the ToppGene database. In GSE55940, 91 downregulated and 151 upregulated DEGs were identified. In GSE46306, 561 overlapping differentially methylated genes were obtained through the differential methylation analysis at the CpG site level, CpG island level and gene level. A total of 5 overlapping genes [dipeptidyl peptidase 4 (DPP4); endothelin 3 (EDN3); fibroblast growth factor 14 (FGF14); tachykinin, precursor 1 (TAC1); and wingless-type MMTV integration site family, member 16 (WNT16)] between the 561 overlapping differentially methylated genes and the 242 DEGs were identified, which were downregulated and hypermethylated simultaneously in cervical cancer samples. Enriched GO terms were receptor binding (involving DPP4, EDN3, FGF14, TAC1 and WNT16), ameboidal-type cell migration (DPP4, EDN3 and TAC1), mitogen-activated protein kinase cascade (FGF14, EDN3 and WNT16) and cell proliferation (EDN3, WNT16, DPP4 and TAC1). These results indicate that DPP4, EDN3, FGF14, TAC1 and WNT16 may be involved in the pathogenesis of cervical cancer.
| S-EPMC4907103 | biostudies-literature
Project description:PurposeThe present study is to discover a new genes associated with drug resistance development in ovarian cancer.MethodsWe used microarray analysis to determine alterations in the level of expression of genes in cisplatin- (CisPt), doxorubicin- (Dox), topotecan- (Top), and paclitaxel- (Pac) resistant variants of W1 and A2780 ovarian cancer cell lines. Immunohistochemistry assay was used to determine protein expression in ovarian cancer patients.ResultsWe observed alterations in the expression of 22 genes that were common to all three cell lines that were resistant to the same cytostatic drug. The level of expression of 13 genes was upregulated and that of nine genes was downregulated. In the CisPt-resistant cell line, we observed downregulated expression of ABCC6, BST2, ERAP2 and MCTP1; in the Pac-resistant cell line, we observe upregulated expression of ABCB1, EPHA7 and RUNDC3B and downregulated expression of LIPG, MCTP1, NSBP1, PCDH9, PTPRK and SEMA3A. The expression levels of three genes, ABCB1, ABCB4 and IFI16, were upregulated in the Dox-resistant cell lines. In the Top-resistant cell lines, we observed increased expression levels of ABCG2, HERC5, IFIH1, MYOT, S100A3, SAMD4A, SPP1 and TGFBI and decreased expression levels of MCTP1 and PTPRK. The expression of EPHA7, IFI16, SPP1 and TGFBI was confirmed at protein level in analyzed ovarian cancer patients..ConclusionsThe expression profiles of the investigated cell lines indicated that new candidate genes are related to the development of resistance to the cytostatic drugs that are used in first- and second-line chemotherapy of ovarian cancer.
| S-EPMC5564819 | biostudies-literature
Project description:More women are delaying child-birth. Thus, the diagnosis of pregnancy-associated breast cancer (PABC) will continue to increase. The aim of this study was to identify core candidate genes of PABC, and the relevance of the genes on the prognosis of PABC. GSE31192 and GSE53031 microarray profile datasets were downloaded from the Gene Expression Omnibus database and differentially expressed genes were analyzed using the R package and GEO2R tool. Then, Gene Ontology and Kyoto Encyclopedia of Gene and Genome pathway enrichment analyses were performed using the Database for Annotation, Visualization, and Integrated Discovery. Moreover, the Search Tool for the Retrieval of Interacting Genes and the Molecular Complex Detection Cytoscape software plug-in were utilized to visualize protein-protein interactions and to screen candidate genes. A total of 239 DEGs were identified in PABC, including 101 up-regulated genes mainly enriched in fatty acid activation and the fibroblast growth factor signaling pathway, while 138 down-regulated genes particularly involved in activation of DNA fragmentation factor and apoptosis-induced DNA fragmentation. Fourteen hub genes with a high degree of connectivity were selected, including CREB1, ARF3, UBA5, SIAH1, KLHL3, HECTD1, MMP9, TRIM69, MEX3C, ASB6, UBE2Q2, FBXO22, EIF4A3, and PXN. Overall survival (OS) analysis of core candidate genes was performed using the Gene Expression Profiling Interactive Analysis and UALCAN websites. High ASB6 expression was associated with worse OS of PABC patients. Molecular subtypes and menopause status were also associated with worse OS for PABC patients. In conclusion, ASB6 could be a potential predictor and therapeutic target in patient with PABC.
| S-EPMC6591572 | biostudies-literature
Project description:The aim of this study was to identify potential microRNAs and genes associated with drug resistance in ovarian cancer through web-available microarrays. The drug resistant-related microRNA microarray dataset GS54665 and mRNA dataset GSE33482, GSE28646, and GSE15372 were downloaded from the Gene Expression Omnibus database. Dysregulated microRNAs/genes were screened with GEO2R and were further identified in SKOV3 (SKOV3/DDP) and A2780 (A2780/DDP) cells by real-time quantitative PCR (qRT-PCR), and then their associations with drug resistance was analyzed by comprehensive bioinformatic analyses. Nine microRNAs (microRNA-199a-5p, microRNA-199a-3p, microRNA-199b-3p, microRNA-215, microRNA-335, microRNA-18b, microRNA-363, microRNA-645 and microRNA-141) and 38 genes were identified to be differentially expressed in drug-resistant ovarian cancer cells, with seven genes (NHSL1, EPHA3, USP51, ZSCAN4, EPHA7, SNCA and PI15) exhibited exactly the same expression trends in all three microarrays. Biological process annotation and pathway enrichment analysis of the 9 microRNAs and 38 genes identified several drug resistant-related signaling pathways, and the microRNA-mRNA interaction revealed the existence of a targeted regulatory relationship between the 9 microRNAs and most of the 38 genes. The expression of 9 microRNAs and the 7 genes by qRT-PCR in SKOV3/DDP and A2780/DDP cells indicating a consistent expression profile with the microarrays. Among those, the expression of EPHA7 and PI15 were negatively correlated with that of microRNA-141, and they were also identified as potential targets of this microRNA via microRNA-mRNA interaction. We thus concluded that microRNA-141, EPHA7, and PI15 might jointly participate in the regulation of drug resistance in ovarian cancer and serve as potential targets in targeted therapies.
| S-EPMC4525906 | biostudies-literature
Project description:Colorectal cancer (CRC) is one of the most prevalent malignancies worldwide and remains the third leading cause of cancer-associated mortality. The present study aimed to fully elucidate the pathogenesis of CRC and identify associated genes in tumor development. Microarray GSE44076, GSE41328 and GSE44861 datasets were downloaded from the Gene Expression Omnibus database and integrated with meta-analysis. Differentially-expressed genes (DEGs) were identified from CRC samples compared with adjacent non-cancerous controls using the Limma package in R, followed by functional analysis using the Database for Annotation, Visualization, and Integrated Discovery online tool. A protein-protein interaction (PPI) network of DEGs and linker genes was constructed using NetBox software and modules were also mined. Functional annotation was performed for modules with a maximum number of nodes. Subsequent to meta-analysis to pool the data, one dataset that included 327 samples involved in 11,081 genes was obtained. A total of 697 DEGs were identified between CRC samples and adjacent non-cancerous controls. In the PPI network, modules 1 and 5 contained the maximum number of nodes. Collagen, type I, ?1 (COL1A1), COL1A2 and matrix metallopeptidase 9 (MMP9) in module 1 and UDP-glucose 6-dehydrogenase (UGDH), aldehyde dehydrogenase 1 family, member A1 (ALDH1A1), fatty acid binding protein 4 (FABP4) and monoglyceride lipase (MGLL) in module 5 exhibited a high degree of connectivity. Functional analysis indicated that the genes in module 1 were involved in extracellular matrix (ECM)-associated functions and that the genes in module 5 were involved in metabolism-related functions. Overall, significant DEGs and linker genes, namely COL1A1, COL1A2, MMP9, UGDH, ALDH1A1, FABP4 and MGLL, play a crucial role in the development of CRC via regulating the ECM and cell metabolism.
| S-EPMC5103929 | biostudies-literature