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Results for “expression atlas”

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PubMed2006

Fibronectin is distinctly downregulated in murine mammary adenocarcinoma cells with high metastatic potential.

In the present work we used a murine mammary cancer model of two related adenocarcinomas with different lung metastasizing abilities, to compare their global gene expression profiles. Clontech Atlas mouse cDNA microarrays of primary cultured tumor cells were employed to identify genes that are modulated in the more metastatic variant MM3 relative to its parental tumor M3. A total of 88 from 1,176 genes were differentially expressed in MM3 primary cultures, most of them (n=86) were upregulated. Genes were grouped according to their functions as associated with signal transduction and transcription regulation (e.g. Stat1 and Zfp 92), with cell adhesion and motility (cadherin 1, fibronectin), with invasion and angiogenesis (uPA, 72 kDa MMP2), with the regulation of cell proliferation and cell death (cyclins G and A2, TNF), and also included growth factors and receptors, oncogenes and tumor suppressors genes (p107, TGFbeta2, TBR-I, PDGFR). Only 2 genes, TTF1 and fibronectin (FN), showed a significant downregulation. Notably FN expression, loss of which has been associated with a malignant phenotype, was reduced about 19-fold in the more metastatic MM3 cells. Previously known differences in expression patterns associated with the metastatic capacity of MM3 and M3 adenocarcinomas, including downregulation of FN or upregulated expression of TGFbeta and proteases, were confirmed by the array data. The fact that FN was one of the only two genes significantly down-regulated out of the 1,176 genes analyzed stresses the hypothesis that FN may behave as an important metastasis suppressor gene in mammary cancer.

Adenocarcinoma↗

PubMed2004

A database for management of gene expression data in situ.

MOTIVATION: To create a spatiotemporal atlas of Drosophila segmentation gene expression at cellular resolution. RESULTS: The expression of segmentation genes plays a crucial role in the establishment of the Drosophila body plan. Using the IBM DB2 Relational Database Management System we have designed and implemented the FlyEx database. FlyEx contains 2832 images of 14 segmentation gene expression patterns obtained from 954 embryos and 2,073,662 quantitative data records. The averaged data is available for most of segmentation genes at eight time points. FlyEx supports operations on images of gene expression patterns. The database can be used to examine the quality of data, analyze the dynamics of formation of segmentation gene expression domains, as well as estimate the variability of gene expression patterns. We also provide the capability to download data of interest. AVAILABILITY: http://urchin.spbcas.ru/flyex, http://flyex.ams.sunysb.edu/flyex

Animals↗

PubMed1994

Atlas morphology in relation to craniofacial morphology and head posture.

The associations between dimensions of the first cervical vertebra, atlas, and a representative set of craniofacial and postural variables were studied on cephalometric radiographs of a sample of 103 adult males aged 22-30 years, recorded in the natural head position (mirror position). Atlas morphology was expressed by nine variables, linear and angular craniofacial dimensions by 27 variables, and head and cervical posture by seven variables. A pattern of low but significant correlations was found. Although the correlations were low, the study confirmed that the dimensions of the atlas vertebra reflect associations between cranio-cervical posture and craniofacial morphology. Negative correlations were found between the height of the posterior arch of atlas and the inclination of the mandible and the maxilla to the anterior cranial base. Low positive correlations between the height of the anterior arch and vertical facial dimensions reflect the general co-ordination of the vertical growth of the face and the cervical column. Moreover, the pattern of correlations between the atlanto-cranial angle and facial morphology suggests that in changes of the cranio-cervical angle, atlas follows the cervical column.

Adult↗

PubMed1997

Sorption of Aluminum to Plasma Membrane Vesicles Isolated from Roots of Scout 66 and Atlas 66 Cultivars of Wheat.

To further elucidate the mechanisms of differential genotypic tolerance to Al, plasma membrane (PM) vesicles were isolated from whole roots, root tips, and tipless roots of Al3+-sensitive and Al3+-tolerant cultivars (cv) of wheat (Triticum aestivum L. cv Scout 66 and cv Atlas 66, respectively). Vesicles from cv Scout root tips sorbed more Al than vesicles prepared from any other source. The intrinsic surface-charge density of vesicles isolated from cv Scout was 26% more negative than vesicles from cv Atlas (-37.2 versus -29.5 millicoulombs m-2). Growth experiments indicated that cv Scout is slightly more sensitive to La3+ than is cv Atlas, that the cultivars are equally sensitive to H+, and that cv Atlas is slightly more sensitive to SeO42-. The difference in sensitivity to Al3+ was very large; for a 50% inhibition, a 16-fold greater activity of Al3+ was required for cv Atlas. Using a newly developed Gouy-Chapman-Stern model for ion sorption to the PM together with growth-response curves, we estimate that the difference in surface-charge density can account for the slightly greater sensitivity of cv Scout to cationic toxicants and the slightly greater sensitivity of cv Atlas to anionic toxicants. According to our estimates the differences in PM surface negativity and Al sorptive capacity probably account for some of the difference in sensitivity to Al3+, but the greater part of the difference probably arises from other tolerance mechanisms expressed in cv Atlas root tips that reduce the amount of Al3+ that can reach the PM.

Journal Article↗

PubMed2001

Identifying differentially expressed genes associated with metastasis of follicular thyroid cancer by cDNA expression array.

Patients with follicular thyroid carcinoma have a higher incidence of metastasis than papillary thyroid carcinoma when thyroid cancer is diagnosed. The cDNA expression array technology is utilized herein to profile differentially expressed genes from metastatic human follicular thyroid carcinoma and reveal new tumor markers as well as target genes for therapeutic intervention. Tissue samples were obtained during surgical resection of the thyroid follicular carcinoma and metastatic tissue in the brain of the same patient. Two identical Atlas human cDNA expression arrays were hybridized with 32P-labeled cDNA probes derived from RNA of either primary thyroid cancer or metastatic tissue. Parallel analysis of the hybridized signals allowed us to identify the alteration of gene expression in the metastasis process. Eighteen genes significantly overexpressed and 40 genes significantly underexpressed were identified in the metastatic thyroid cancer. Genes that displayed an altered expression were associated with the processes of cell cycle regulation, apoptosis, DNA damage response, angiogenesis, cell adhesion and mobility, invasion, and immune response. An expression profile of genes that are associated with metastasis process of follicular thyroid cancer was also discussed. Further investigation is required to understand the precise relationship between the altered expression of these genes and the metastasis process of follicular thyroid cancer.

Adenocarcinoma, Follicular↗

PubMed2001

Gene expression analysis in N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mice model of Parkinson's disease using cDNA microarray: effect of R-apomorphine.

To establish the possible roles of oxidative stress, inflammatory processes and other unknown mechanisms in neurodegeneration, we investigated brain gene alterations in N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mice model of Parkinson's disease using Atlas mouse cDNA expression array membrane. The expression of 51 different genes involved in oxidative stress, inflammation, glutamate and neurotrophic factors pathways as well as in still undefined processes, such as cell cycle regulators and signal transduction molecules, was differentially affected by the treatment. The present study indicates the involvement of an additional cascade of events that might act in parallel to oxidative stress and inflammation to converge eventually into a common pathway leading to neurodegeneration. The attenuation of these gene changes by R-apomorphine, an iron chelator-radical scavenger drug, supports our previous findings in vivo where R-apomorphine was neuroprotective.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed2003

SMART amplification maintains representation of relative gene expression: quantitative validation by real time PCR and application to studies of alcoholic liver disease in primates.

The small quantities of tissue available for most studies of human disease are a significant limitation for meaningful gene expression profiling. The Atlas Switch Mechanism At the 5' end of Reverse Transcript (SMART) probe amplification kit uses as little as 50 ng of total RNA to generate complex cDNA probes for DNA array and other analyses. However, the extent to which this attractive methodology maintains representation of relative gene expression has not been quantified. In this study, we demonstrate using real-time quantitative PCR analysis that the relative expression levels of a range of low- to high-abundance mRNAs are retained after SMART amplification independent of transcript abundance and full-length transcript, coding region and PCR product size. Using this technology, a mean amplification of 3800-fold was achieved in human liver samples, greatly enhancing the ability to perform replicate DNA array experiments. Probes generated with the SMART amplification method were used to detect increased expression of genes involved with inflammation, fibrosis, xenobiotic metabolism, immune function, oxidant stress and endothelium in liver from the baboon model of alcoholic liver disease.

DNA, Complementary↗

PubMed2002

[Plerosis of cDNA array of normal human nasopharyngeal tissue and nasopharyngeal carcinoma].

OBJECTIVE: To compare gene expression gene profile of nasopharyngeal carcinoma (NPC) tissue with that of normal nasopharyngeal tissues by cDNA array and to discuss possible functions of DNA repair-related genes in NPC tissue. METHODS: After hybridization of atlas human cancer cDNA expression array 7742 - 1, atlas hybridization results were analyzed by Atlas Image 1.01 a software package. Using RT-PCR was used to confirm the results. RESULTS: Of 63 differentially expressed genes in quadrangle C including DNA damage response, repair & recombination-related genes, 6 DNA repair-related genes were up-regulated, 12 were down-regulated. CONCLUSION: DNA repair-related genes may be involved in patho-physiological process of nasopharyngeal carcinoma.

DNA Repair↗

PubMed2002

Two forms of gonadotropin-releasing hormone (GnRH) are expressed in human breast tissue and overexpressed in breast cancer: a putative mechanism for the antiproliferative effect of GnRH by down-regulation of acidic ribosomal phosphoproteins P1 and P2.

Gonadotropin-releasing hormone (GnRH) analogues are used for the treatment of breast, prostate, and ovarian cancer. These analogues exert their antitumor effects indirectly by inhibiting the pituitary-gonadal axis, as well as by direct inhibition of proliferation of human breast cancer cells. However, the molecular mechanisms mediating these direct antiproliferative effects are not fully understood. We found that normal and malignant human breast tissue express two forms of the neuropeptide GnRH. Quantitative reverse transcription-PCR shows that mRNA encoding the GnRH-I and GnRH-II peptides are overexpressed in cancerous versus normal tissues obtained from the same patients. To elucidate the function of these peptides in breast cancer cells, we used the atlas human cDNA expression arrays technology and studied the differentially regulated genes after GnRH treatment of MCF-7 cells. We found that a wide range of GnRH-I or GnRH-II concentrations (0.1-10 nM) inhibit the expression of mRNA encoding the 60S acidic ribosomal phosphoproteins, P1 and P2. These results were confirmed by quantitative reverse transcription-PCR, as well as Western blot analysis and immunofluorescence staining. The P1 and P2 proteins interact with elongation factors EF1 and EF2, and the level of their phosphorylation is one of the regulatory mechanisms for the overall rate of protein elongation. Thus, reduced expression of P1 and P2 proteins can affect the rate of protein translation, thereby decreasing proliferation rate of cells. Our studies may therefore suggest a putative mechanism for the direct antiproliferative effect of GnRH in breast cancer cells.

Breast↗

PubMed2005

Gene expression profile of amyloid beta protein-injected mouse model for Alzheimer disease.

AIM: To investigate the gene expression profile changes in the cerebral cortex of mice injected icv with amyloid beta-protein (Abeta) fragment 25-35 using cDNA microarray. METHODS: Balb/c mice were randomly divided into a control group and Abeta-treated group. The Morris water maze test was performed to detect the effect of Abeta-injection on the learning and memory of mice. Atlas Mouse 1.2 Expression Arrays containing 1176 genes were used to investigate the gene expression pattern of each group. RESULTS: The gene expression profiles showed that 19 genes including TBX1, NF-kB, AP-1/c-Jun, cadherin, integrin, erb-B2, and FGFR1 were up-regulated after 2 weeks of icv administration of Abeta; while 12 genes were down-regulated, including NGF, glucose phosphate isomerase 1, AT motif binding factor 1, Na+/K+-ATPase, and Akt. CONCLUSIONS: The results provide important leads for pursuing a more complete understanding of the molecular events of Abeta-injection into mice with Alzheimer disease.

Alzheimer Disease↗

PubMed2025

COL5A1 in the tumor microenvironment predicts the prognosis of head and neck cancer.

ObjectivesThis study aims to investigate the significance of tumor microenvironment (TME)-related genes and signal transduction pathways in head and neck cancer (HNC).MethodsGene expression and clinical data of HNC patients were obtained from the Cancer Genome Atlas (TCGA) database. Differentially expressed genes (DEGs) were screened through a multi-step filtration approach to obtain candidate predictors. The biological role of COL5A1 in HNC was verified through rigorous bioinformatic analysis, experimental validation using quantitative real-time PCR (qRT-PCR), immunohistochemical (IHC) analysis from HNC samples, and IHC data from the Human Protein Atlas (HPA) database.ResultsCOL5A1 was significantly upregulated in HNC tissues and cell lines. High COL5A1 expression was significantly associated with advanced tumor grade (P < .05) and shorter survival (TCGA: P < .001; GSE42743: P = .004). COL5A1 was an independent prognostic indicator (univariate analysis: HR = 1.324, P = .001; Multivariate analysis: HR = 1.326, P = .005). It was enriched in pathways related to tumor invasion and immune responses, and its expression was associated with decreased levels of CD8+ T cells and increased levels of macrophages and neutrophils. Spatial distribution analysis revealed higher expression at the tumor's leading edge (vs. tumor core: P < .001). COL5A1 expression is associated with tumor stage, with more pronounced expression in advanced-stage tumors.ConclusionCOL5A1 represented a novel potential prognostic indicator and therapeutic target in an HNC database sample, as its expression is closely linked to tumor progression, immune cell infiltration, and adverse clinical outcomes. These findings, primarily derived from squamous cell carcinoma-dominated cohorts, warrant further functional validation.

Humans↗

PubMedDate not supplied

The development and evolution of insect mouthparts as revealed by the expression patterns of gnathocephalic genes.

To understand better both the development and evolution of insect mouthparts, we have compared the expression pattern of several developmentally important genes in insects with either mandibulate or stylate-haustellate mouthparts. Specifically, we examined the expression of the proboscipedia (pb) and Distal-less (Dll) gene products as well as three regulators of pb, Sex combs reduced (Scr), Deformed (Dfd), and cap 'n' collar (cnc). These genes are known to control the identity of cells in the gnathal segments of Drosophila melanogaster and would appear to have similar conserved functions in other insects. Together we have made an atlas of gene expression in the heads of three insects: Thermobia domestica and Acheta domestica, which likely exemplify the mandibulate mouthparts present in the common insect ancestor, and Oncopeltus fasciatus, which has piercing-sucking mouth parts that are typical of the Hemiptera. At the earliest stages of embryogenesis, only the expression of pb was found to differ dramatically between Oncopeltus and the other insects examined, although significant differences were observed later in development. This difference in pb expression reflects an apparent divergence in the specification of gnathal identity between mandibulate and stylate-haustellate mouthparts, which may result from a "phylogenetic homeosis" that occurred during the evolution of the Hemiptera.

Amino Acid Sequence↗

PubMed2001

Application of complementary DNA microarray (DNA chip) technology in the study of gene expression profiles during folliculogenesis.

OBJECTIVE: Using oligonucleotide microarray (DNA chip)-based hybridization analysis to gain a comprehensive view of gene expression and regulation involved in folliculogenesis. DESIGN: Prospective randomized study. SETTING: Academic institution. ANIMAL(S): B6D2F1 female mice. INTERVENTION(S): Superovulation. MAIN OUTCOME MEASURE(S): Preantral follicles isolated from day 14 B6D2F-1 mice were stimulated in vitro to form Graafian follicles. Total RNA extracted from the mouse preantral and Graafian follicles were reverse transcribed, labeled with digoxigenin-11-dUTP, and then hybridized with Clontech Atlas mouse cDNA expression arrays for comparison. RESULT(S): Of 588 known studied genes, 39 and 61 were detected in preantral follicles and in Graafian follicles, respectively, and 17 were highly expressed consistently in both preantral and Graafian follicles. Performing clustering analysis, we found that 15 detected genes were down-regulated and 46 were up-regulated as the follicles advanced to mature stages. CONCLUSION(S): We have successfully developed a sensitive DNA chip technology that is able to simultaneously and quantitatively study gene expression profiles in a small number of follicles (1.5-15 follicles). Several folliculogenesis-related genes have been identified. Some of these genes were expressed, indicating that they may be essential for follicle growth and maturation, whereas others were up-regulated only during late follicular development, indicating stage-specific roles.

Animals↗

PubMed2002

Insulin-like growth factor binding protein-3 is upregulated in LPS-treated THP-1 cells.

BACKGROUND: Lipopolysaccharide (LPS) is a potent activator of human monocytic cells. We have determined that LPS stimulation of the human monocytic cell line, THP-1, results in an increased apoptotic rate. We hypothesized that cDNA expression array analysis could be used to identify target genes involved in the regulation of this process. METHODS: THP-1 cells (1 x 10(6)/mL) were stimulated with LPS (1 microg/mL) or vehicle control. Apoptosis was measured at 0, 24, 48, 72 and 96 h using propidium iodide staining and flow cytometry to determine the percentage of cells with hypodiploid DNA. At 16 h, the Atlas Human cDNA expression array system, containing probes for 205 genes related to apoptosis, was used to survey and quantify transcript expression. The experiment was performed in duplicate and the membranes were normalized to cytoplasmic beta-actin. Standard Western blotting was performed on the conditioned medium to correlate secreted protein expression with RNA expression. Pretreatment with insulin-like growth factor I (IGF-I) was performed to determine whether the effects of insulin-like growth factor binding protein-3 (IGFBP-3) on apoptosis were IGF-dependent. RESULTS: LPS stimulation of THP-1 cells resulted in a greater than 2-fold increase in the rate of apoptosis when compared to vehicle control. When the cDNA expression arrays were compared, there was a 500-fold increase in the expression of the IGFBP-3 transcript in the LPS-stimulated cells. Western blotting of culture medium verified an approximately 2-fold increase in secreted IGFBP-3. Pretreatment with IGF-I did not prevent the increase in apoptosis seen with LPS stimulation. CONCLUSIONS: THP-1 cell apoptosis is increased in response to LPS stimulation and is associated with a significant induction of IGFBP-3 mRNA and protein. IGFBP-3, which reportedly promotes apoptosis and modulates the bioavailability of the pro-survival insulin-like growth factor 1, may serve to regulate apoptosis in monocytic cells in an IGF-independent manner. These data further support the investigation of the role of the IGF axis in programmed cell death of immune cells.

Apoptosis↗

PubMed2001

A CREB site in the BRCA1 proximal promoter acts as a constitutive transcriptional element.

Transcriptional regulation of the BRCA1 proximal promoter has been suggested to play a role in the decreased expression of BRCA1 observed in sporadic breast cancer. Computer analysis of the sequence of the proximal promoter reveals the presence of a potential CREB site. We have identified CREB/ATF-1 as the factor interacting with this site in nuclear extracts from MCF-7 and T-47D cells. This site is shown to be important for the constitutive expression of the promoter in these cells, as well as in Hep G2 cells. Despite the presence of this site, the BRCA1 promoter is not responsive to cAMP induction. It appears that CREB acts as a constitutive positive element for BRCA1 expression and that any mechanism inactivating CREB function would have a dramatic effect on BRCA1 expression.

Activating Transcription Factor 1↗

PubMed2025

Identification and validation of prognostic genes associated with mitochondrial nuclear genes in gastric cancer.

Mitochondrial-related nuclear genes (MNGs) have shown great importance in cancer diagnosis and prognosis, but their role in gastric cancer (GC) remains unclear. GC-related transcriptome data from the gene expression omnibus and cancer genome atlas databases were analyzed to identify differentially expressed MNGs. A prognostic risk model was constructed through univariate Cox and least absolute shrinkage and selection operator regression, validated by Kaplan-Meier (K-M) survival curve and receiver operating characteristic curve. This was followed by immune infiltration analysis, independent prognostic analysis, functional enrichment analysis, drug sensitivity analysis, drug prediction, molecular docking and construction of regulatory networks. Three prognostic genes (ATP8A2, COX15 and TARS2) were identified. The expression of TARS2 and COX15 was positively correlated with CNV, while ATP8A2 was unaffected. The risk model and nomogram, integrating risk score and clinicopathological factors, exhibited excellent predictive performance. A significant correlation was observed between prognostic genes and differential immune cells, such as T cells, B cells, and NK cells. BMS-754807, Gefitinib, JQ1, Lapatinib, and Sapitinib exhibited significant differences in sensitivity between the high-risk group and the low-risk group. The results of molecular docking showed TP8A2 has stable binding ability with cytosine, COX15 with indomethacin, and TARS2 with bisacodyl. RT-qPCR revealed downregulation of ATP8A2 and upregulation of COX15 and TARS2 in GC samples. MNGs, including ATP8A2, COX15, and TARS2, demonstrated significant associations with immune infiltration, CNV, and prognostic outcomes of GC.

Humans↗

PubMed2006

Uneven size distribution of mammalian genes in the number of tissues expressed and in the number of co-expressed genes.

Tissue specificity, the traditional predictor of gene function, has recently been used to interpret the selective pressure associated with gene architecture. In this work, we examine gene structures and their relation to the number of tissues expressed and to the number of co-expressed genes, using a recent atlas of microarray-based mouse gene expression in 55 normal tissues. We define tissue specificity and expression-pattern specificity according to the number of tissues expressed and the number of co-expressed genes, respectively. We find that, consistent with previous findings, tissue non-specific (housekeeping) genes are short in all gene regions (coding regions, intron, 5' and 3' untranslated regions). However, in contrast to previous suggestion that tissue-specific genes are long, the genes that are the most tissue-specific (expressed only in one tissue) are also short. We further show that both expression-pattern-specific and non-specific genes are long in coding and non-coding regions. The origins for short tissue-specific genes and long expression-pattern-specific genes are not clear. Genes with highly non-specific expression patterns (i.e. genes with a large number of co-expressed genes) are composed of genes that spread all tissues but are overwhelmingly enriched in the central nervous system (e.g. brain). Thus, the large sizes of these genes are possibly related to the functional complexity and/or accelerated evolutions of the central nervous system.

Animals↗

PubMed2026

ERP44 Is Associated With Poor Prognosis and Promotes Proliferation and Temozolomide Resistance in Lower-grade Glioma.

BACKGROUND/AIM: Endoplasmic reticulum resident protein 44 (ERP44), a protein disulfide isomerase family member, has been implicated in tumor biology, but its role in lower-grade glioma (LGG) remains unclear. This study investigated the prognostic significance and biological function of ERP44 in LGG, focusing on proliferation and temozolomide (TMZ) resistance. MATERIALS AND METHODS: ERP44 expression, clinicopathological associations, and prognostic value were analyzed using The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Chinese Glioma Genome Atlas (CGGA) datasets. Time-dependent receiver operating characteristic (ROC) curves, Cox regression, and a prognostic nomogram were constructed. Differential expression, Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO) enrichment, immune infiltration, and drug sensitivity analyses were performed. Functional validation was conducted in SW1088 and SW1783 cells using shRNA-mediated ERP44 knockdown, followed by RT-qPCR, western blotting, CCK-8, colony formation, and TMZ IC50 assays. Subcutaneous xenograft models with or without TMZ treatment were used for in vivo validation. RESULTS: ERP44 was markedly upregulated in LGG and associated with higher WHO grade, IDH wildtype status, 1p/19q non-codeletion, and poor survival in TCGA and CGGA cohorts. ERP44 showed strong prognostic performance and improved risk stratification in a multivariable nomogram. Enrichment analyses linked high ERP44 expression to immune/inflammatory pathways and reduced neuronal functional signatures. ERP44 positively correlated with immune infiltration, proliferation/stemness markers, and predicted TMZ resistance, while its knockdown inhibited proliferation and colony formation, reduced TMZ IC50, suppressed xenograft growth, enhanced TMZ efficacy, and decreased Ki67 positivity. CONCLUSION: ERP44 is a prognostic biomarker that promotes LGG proliferation and TMZ resistance, suggesting its potential as a therapeutic target.

Humans↗