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Results for “Gene Expression Profiling”

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PubMed2005

Gene expression profile differences in gastric cancer, pericancerous epithelium and normal gastric mucosa by gene chip.

AIM: To study the difference of gene expression in gastric cancer (T), pericancerous epithelium (P) and normal tissue of gastric mucosa (C), and to screen an associated novel gene in early gastric carcinogenesis by oligonucleotide microarray. METHODS: U133A (Affymetrix, Santa Clara, CA) gene chip was used to detect the gene expression profile difference in T, P and C, respectively. Bioinformatics was used to analyze the detected results. RESULTS: When gastric cancer was compared with normal gastric mucosa, 766 genes were found, with a difference of more than four times in expression levels. Of the 766 genes, 530 were up-regulated (Signal Log Ratio (SLR) >2), and 236 were down-regulated (SLR<-2). When pericancerous epithelium was compared with normal gastric mucosa, 64 genes were found, with a difference of more than four times in expression levels. Of the 64 genes, 50 were up-regulated (SLR>2), and 14 were down-regulated (SLR<-2). Compared with normal gastric mucosa, a total of 143 genes with a difference in expression levels (more than four times, either in cancer or in pericancerous epithelium) were found in gastric cancer (T) and pericancerous epithelium (P). Of the 143 genes, 108 were up-regulated (SLR>2), and 35 were down-regulated (SLR<-2). CONCLUSION: To apply a gene chip could find 143 genes associated with the genes of gastric cancer in pericancerous epithelium, although there were no pathological changes in the tissue slices. More interesting, six genes of pericancerous epithelium were up-regulated in comparison with genes of gastric cancer and three genes were down-regulated in comparison with genes of gastric cancer. It is suggested that these genes may be related to the carcinogenesis and development of early gastric cancer.

Epithelium↗

PubMed2004

ApcMin/+ mouse model of colon cancer: gene expression profiling in tumors.

The Apc(Min/+) mouse is a popular animal model for studies of human colon cancer, but the molecular changes associated with neoplasia in this system have only been partially characterized. Our aim was to identify novel genes involved in tumorigenesis in this model. RNA from intestinal adenomas and from pre-neoplastic small intestine were prepared from six Apc(Min/+) mice. The tumor transcriptomes were analyzed with high-density oligonucleotide microarrays representing approximately 12,000 probe sets; we compared their profiles with those of matched pre-neoplastic intestine. Stringent analysis revealed reproducible changes for 98 probe sets representing 90 genes, including novel observations regarding 50 genes whose involvement in this mouse model has never been reported. In addition to the expected changes in growth regulatory genes, the altered gene products could be assigned to four functional groupings that should enhance tumorigenesis: metabolic changes that would result in a high rate of glycolysis, alterations in enzymes involved in reactive oxygen species or carcinogen metabolism, cytoskeletal elements, and proteins involved in tumor invasion or angiogenesis. A fifth group consisted of expression changes that might restrict tumor progression, suggesting that the adenomatous state reflects a balance of pro- and anti-tumorigenic factors. Since many of the altered genes had not previously been reported to be involved in any tumorigenic processes, our observations provide a host of new candidates for potential modulation to prevent or treat intestinal neoplasia.

Adenomatous Polyposis Coli Protein↗

PubMed2003

MLL-mediated transcriptional gene regulation investigated by gene expression profiling.

The human mixed lineage leukemia (MLL) gene is involved in about 50 different chromosomal translocations, associated with the disease phenotype of acute leukemia. However, the normal function of MLL is less understood. Homozygous knockouts of murine Mll were embryonal lethal, while heterozygous disruption led to aberrant hox gene expression associated with skeletal malformations, growth retardation, and impaired hematopoiesis. To understand MLL functions on the molecular level, gene expression profiling experiments were performed with a pair of murine cell lines (MLL(+/+) and MLL(-/-)). Microarray hybridization experiments revealed 197 potential target genes that are differentially expressed, providing new and important clues about MLL functions.

Animals↗

PubMedDate not supplied

Gene expression profiles of microvascular endothelial cells after stimuli implicated in the pathogenesis of vasoocclusion.

Altered gene expression in endothelial cells interacting with sickle red blood cells (RBC) and other blood components, in particular the pro-inflammatory cytokines, is an essential step in the pathogenesis of vasoocclusive crises in sickle cell disease (SCD). Using cDNA arrays, we monitored gene expression profiles of human lung microvascular endothelial cells (HMVEC-L) after stimuli that are likely involved in the pathogenesis of vasoocclusion. We detected increased expression of multiple genes in HMVEC-L after their exposure to pro-inflammatory cytokines TNFalpha and IL-1beta and to RBC with increased external exposure of phosphatidylserine and RBC from a patient with SC hemoglobin. While some of these genes have previously been implicated in vascular damage, many represent new targets for investigation of the pathogenesis of vasoocclusion in SCD.

Cells, Cultured↗

PubMed2005

Gene-expression profiling of White spot syndrome virus in vivo.

White spot syndrome virus, type species of the genus Whispovirus in the family Nimaviridae, is a large, double-stranded DNA (dsDNA) virus that infects crustaceans. The genome of the completely sequenced isolate WSSV-TH encodes 184 putative open reading frames (ORFs), the functions of which are largely unknown. To study the transcription of these ORFs, a DNA microarray was constructed, containing probes corresponding to nearly all putative WSSV-TH ORFs. Transcripts of 79 % of these ORFs could be detected in the gills of WSSV-infected shrimp (Penaeus monodon). Clustering of the transcription profiles of the individual genes during infection showed two major classes of genes: the first class reached maximal expression at 20 h post-infection (p.i.) (putative early) and the other class at 2 days p.i. (putative late). Nearly all major and minor structural virion-protein genes clustered in the latter group. These data provide evidence that, similar to other large, dsDNA viruses, the WSSV genes at large are expressed in a coordinated and cascaded fashion. Furthermore, the transcriptomes of the WSSV isolates WSSV-TH and TH-96-II, which have differential virulence, were compared at 2 days p.i. The TH-96-II genome encodes 10 ORFs that are not present in WSSV-TH, of which at least seven were expressed in P. monodon as well as in crayfish (Astacus leptodactylus), suggesting a functional but not essential role for these genes during infection. Expression levels of most other ORFs shared by both isolates were similar. Evaluation of transcription profiles by using a genome-wide approach provides a better understanding of WSSV transcription regulation and a new tool to study WSSV gene function.

Animals↗

PubMed2005

Adding semantics to gene expression profiles: new tools for drug discovery.

Gene expression profiles are unveiling a wealth of new potential drug targets for a wide range of diseases, offering new opportunities for drug discoveries. The emerging challenge, however, is the effective selection of the myriad of targets to identify those with the most therapeutic utility. Numerical clustering has became a commonly used method to investigate and interpret gene expression data sets but it is often inadequate to infer the genes' and proteins' role and point to candidate genes for drug development. This review illustrates how clustering methods based on semantic characteristics, such as gene ontologies, could be used to extract more knowledge from genomic data and improve drug target and discovery processes.

Animals↗

PubMed2004

Antigen-specific gene expression profiles of peripheral blood mononuclear cells do not reflect those of T-lymphocyte subsets.

Advances in microarray technology have allowed for the monitoring of thousands of genes simultaneously. This technology is of particular interest to immunologists studying infectious diseases, because it provides tremendous potential for investigating host-pathogen interactions at the level of immune gene expression. To date, many studies have focused either on cell lines, where the physiological relevance is questionable, or on mixed cell populations, where the contributions of individual subpopulations are unknown. In the present study, we perform an intrasubject comparison of antigen-stimulated immune gene expression profiles between a mixed population of peripheral blood mononuclear cells (PBMC) and the two predominant cell types found in PBMC, CD4+ and CD8+ T lymphocytes. We show that the microarray profiles of CD4+ and CD8+ T lymphocytes differ from each other as well as from that of the mixed cell population. The independence of the gene expression profiles of different cell types is demonstrated with a ubiquitous antigen (Candida albicans) as well as with a disease-specific antigen (human immunodeficiency virus p24). This study has important implications for microarray studies of host immunity and underscores the importance of profiling the expression of specific cell types.

Antigens↗

PubMed2005

Gene expression profiling in INS-1 cells overexpressing thioredoxin-interacting protein.

Thioredoxin-interacting protein (TXNIP) is overexpressed in diabetes and has deleterious effects on pancreatic beta-cells and the cardiovascular system. TXNIP is a regulator of the cellular redox state, but has also been suggested to act as a transcriptional repressor. However, the genes and pathways regulated by TXNIP remain unknown. We therefore compared gene expression in INS-1 insulinoma beta-cells overexpressing TXNIP and control LacZ-overexpressing cells using the Affymetrix 230A rat chip. Analysis with the Bayes methodology revealed 98 differentially expressed genes, 90 of which were down-regulated, consistent with the predicted role of TXNIP as a repressor. Using the PathwayAssist software, we found that affected genes were involved in cell death/survival and insulin secretion, and confirmed these findings by real-time RT-PCR and by functional studies. Thus, aside from regulating the cellular redox, TXNIP does modulate overall gene transcription and thereby may further enhance beta-cell death and impair insulin secretion.

Carrier Proteins↗

PubMed2004

Gene expression profiles in the cellular response to a multinuclear platinum complex.

We used cDNA arrays to monitor modulation of mRNA expression after exposure to a multinuclear platinum complex (BBR3464) in a human cervix squamous cell carcinoma cell line (A431) and in a cisplatin-resistant subline (A431/Pt) exhibiting collateral sensitivity to BBR3464. In parental A431cells, the drug induced at least twofold up-regulation of 15 genes including cell cycle and growth regulators, tumor suppressors and signal transduction genes. In cisplatin-resistant A431/Pt cells, BBR3464increased the expression of 15 genes such as apoptosis regulators and genes involved in the DNA damage response. Interestingly, BBR3464induced up-regulation of anti-metastatic factors together with down-regulation of several pro-metastatic factors. Cell cycle analysis indicated a marked G2arrest in treated A431cells, whereas an apoptotic response was documented in A431/Pt cells. These differential patterns of transcriptional profile in sensitive and resistant cells are consistent with a role for cell cycle regulation in the response to BBR3464.

Antineoplastic Agents↗

PubMed2005

[Analysis of gene expression profile of G1/S transition in gastric cancer cell cycle].

OBJECTIVE: To detect the variation of gene expression profile of G1/S transition and elucidate the role of related genes regulating cell cycle from G1 to S phase in gastric cancer. METHODS: Nocodazole-thymidine and double thymidine methods were used to synchronize gastric cells at G2/M and G1/S point, cDNA microarray chips was applied to examine the gene expression profile at G1 early and late phase, S early and late phase during the cell cycle, hierarchy analysis was conducted by a professional software package. RESULTS: A total of 2001 genes were detected available, 959 genes appeared to be upregulated or downregulated, including 147 genes upregulated at G1 late phase. These 147 genes are involved in DNA metabolism, transcription and translation,posttranslational modification, ubiquitination, signal transduction etc, which all affected cell cycle from different aspects. CONCLUSION: Complex multiple gene processes, such as DNA metabolism, transcription and translation, posttranslational modification, ubiquitination, signal transduction etc,are implicated in and also essential for G1/S transition during gastric cancer cell cycle, part of these genes are significantly associate with overproliferation in gastric cancer.

Cell Division↗

PubMed2006

Gene expression profiling of ovarian tissues for determination of molecular pathways reflective of tumorigenesis.

Ovarian cancer is the fourth leading cause of gynecological cancer death among women in the United States. Early detection is a critical prerequisite to initiating effective cancer therapy. Gene microarray technology and proteomics have provided much of the biomarkers with potential use for diagnosis. However, more research is needed to fully understand disease onset and progression. To this end, we have performed microarray analysis with the goal of identifying molecular interaction networks defining tumor growth. Microarray analysis was performed on a limited set of ovarian tissues with various pathological diagnoses using Human Genome Focus Array (HGFA) for the detection of approximately 8500 human transcripts. Hierarchical clustering identified groups of ovarian tissues reflective of low malignant potential/early cancer onset and possible pre-cancerous stages involving small molecule, cytokine and/or hormone-dependent feed-back responses specific to the pelvic reproductive system and a priori initiated tumor suppression mechanisms. ANOVA followed by post hoc Scheffe confirmed our hypotheses. Moreover, we established a protein/protein interaction database associated with HGFA probe sets. This database was used to build and visualize molecular networks integrating small but significant changes in gene expression. In conclusion, we were able for the first time to delineate an intersecting genetic pattern linking ovarian tissues reflective of low potential malignancy/early cancer onset stages via long distance signaling between tissues of gynecological origin.

Case-Control Studies↗

PubMed2002

Gene expression profile analysis in human hepatocellular carcinoma by cDNA microarray.

We performed gene expression profiling of normal and hepatocellular carcinoma (HCC) liver tissues using a high-density microarray that contained 3,063 human cDNA. The results of a microarray hybridization experiment from eight different HCC tissues were analyzed and classified by the Cluster program. Among these differentially-expressed genes, the galectin-3, serine/threonine kinase SGK, translation factor eIF-4A, -4B, -3, fibroblast growth factor receptor, and ribosomal protein L35A were up-regulated; the mRNAs of Nip3, decorin, and the insulin-like growth factor binding protein-3 were down-regulated in HCC. The differential expression of these genes was further confirmed by an RT-PCR analysis. In addition, our data suggest that the gene expression profile of HCC varies according to the histological types.

Carcinoma, Hepatocellular↗

PubMedDate not supplied

Gene expression profiles of hepatoma cell line BEL-7402.

BACKGROUND/AIMS: To investigate the gene expression of cancer related genes in hepatoma cell line BEL-7402 through the usage of Atlas Human Cancer Array with 588 well-characterized human genes related with cancer biology. METHODOLOGY: Hybridization of cDNA membrane was performed with 32P-labeled cDNA probes synthesized from RNA isolated from Human hepatoma cell line BEL-7402 and non-cirrhotic normal liver which was liver transplantation donor. Bioinformatics was used to analyze the result. The reverse transcription polymerase chain reaction of 24 pairs of specimens and northern blot of 4 pairs of specimens were used to confirm the expression pattern of some genes identified by Atlas arrays hybridization. RESULTS: The differential expression cell cycle/growth regulator in hepatoma cell line BEL-7402 showed a stronger tendency toward cell proliferation with up-regulation of E2F-3 and TFDP-2. The anti-apoptotic factors such as Akt-1 were up-regulated. Whereas the promotive genes of apoptosis were down-regulated, such as BAK and caspase-3. Besides this, some genes were up-regulated, such as Integrin beta 8, DNA-PK, CSPCP, cyclin C etc. A number of genes were down-regulated, which included LAR, ABL2, SKY, TDGF1 etc. In general, expression of the cancer progression genes were up-regulated, while expression of anti-cancer progression genes were down-regulated. The results of reverse transcription polymerase chain reaction of 24 pairs of specimens and Northern Blot of 4 pairs of specimens were consistent with the expression pattern of some genes identified by Atals arrays hybridization. CONCLUSIONS: Investigation of gene expression profile of hepatoma cell line BEL-7402 should help to disclose the molecular mechanism of the onset, progression and prognosis of hepatocellular carcinoma. The quick and high-throughout method of profiling gene expression by cDNA array provides us with an overview of key factors that may be involved in hepatocellular carcinoma, and may find the clue to the study of hepatocellular carcinoma carcinogenesis and molecular targets of diagnosis and therapy.

Carcinoma, Hepatocellular↗

PubMed2006

Meta-analysis and meta-review of thyroid cancer gene expression profiling studies identifies important diagnostic biomarkers.

PURPOSE: An estimated 4% to 7% of the population will develop a clinically significant thyroid nodule during their lifetime. In many cases, preoperative diagnoses by needle biopsy are inconclusive. Thus, there is a clear need for improved diagnostic tests to distinguish malignant from benign thyroid tumors. The recent development of high-throughput molecular analytic techniques should allow the rapid evaluation of new diagnostic markers. However, researchers are faced with an overwhelming number of potential markers from numerous thyroid cancer expression profiling studies. MATERIALS AND METHODS: To address this challenge, we have carried out a comprehensive meta-review of thyroid cancer biomarkers from 21 published studies. A gene ranking system that considers the number of comparisons in agreement, total number of samples, average fold-change and direction of change was devised. RESULTS: We have observed that genes are consistently reported by multiple studies at a highly significant rate (P < .05). Comparison with a meta-analysis of studies reprocessed from raw data showed strong concordance with our method. CONCLUSION: Our approach represents a useful method for identifying consistent gene expression markers when raw data are unavailable. A review of the top 12 candidates revealed well known thyroid cancer markers such as MET, TFF3, SERPINA1, TIMP1, FN1, and TPO as well as relatively novel or uncharacterized genes such as TGFA, QPCT, CRABP1, FCGBP, EPS8 and PROS1. These candidates should help to develop a panel of markers with sufficient sensitivity and specificity for the diagnosis of thyroid tumors in a clinical setting.

Biomarkers, Tumor↗

PubMed2004

Differential gene expression profiles of radioresistant oesophageal cancer cell lines established by continuous fractionated irradiation.

Radiation therapy is a powerful tool for the treatment of oesophageal cancer. We established radioresistant cell lines by applying fractionated irradiation in order to identify differentially expressed genes between parent and radioresistant cells. Six oesophageal cancer cell lines (TE-2, TE-5, TE-9, TE-13, KYSE170, and KYSE180) were treated with continuous 2 Gy fractionated irradiation (total dose 60 Gy). We compared expression profiles of each parent and radioresistant lines on a cDNA microarray consisting of 21168 genes. In the fractionated irradiation trial, four radioresistant sublines (TE-2R, TE-9R, TE-13R, KYSE170R) were established successfully, and we identified 19 upregulated and 28 downregulated genes common to radioresistant sublines. Upregulated genes were associated with apoptosis and inflammatory response (BIRC2 and COX-2), DNA metabolism (CD73), and cell growth (PLAU). Downregulated genes were associated with apoptosis (CASP6), cell adhesion (CDH1 and CDH3), transcription (MLL3), and cell cycle (CDK6). Some of these genes were known to be associated with radiation response, such as COX-2, but others were novel. Reverse transcription-polymerase chain reaction confirmed that genes selected by cDNA microarray were overexpressed in clinical specimens of radioresistant cases. Global gene analysis of radioresistant sublines may provide new insight into mechanisms of radioresistance and effective radiation therapy.

Biomarkers, Tumor↗

PubMed2006

Gene expression profiling following constitutive activation of MEK1 and transformation of rat intestinal epithelial cells.

BACKGROUND: Constitutive activation of MEK1 (caMEK) can induce the oncogenic transformation of normal intestinal epithelial cells. To define the genetic changes that occur during this process, we used oligonucleotide microarrays to determine which genes are regulated following the constitutive activation of MEK in normal intestinal epithelial cells. RESULTS: Microarray analysis was performed using Affymetrix GeneChip and total RNA from doxycycline inducible RIEtiCAMEK cells in the presence or absence of doxycycline. MEK-activation induced at least a three-fold difference in 115 gene transcripts (75 transcripts were up-regulated, and 40 transcripts were down-regulated). To verify whether these mRNAs are indeed regulated by the constitutive activation of MEK, RT-PCR analysis was performed using the samples from caMEK expressing RIE cells (RIEcCAMEK cells) as well as RIEtiCAMEK cells. The altered expression level of 69 gene transcripts was confirmed. Sixty-one of the differentially expressed genes have previously been implicated in cellular transformation or tumorogenesis. For the remaining 8 genes (or their human homolog), RT-PCR analysis was performed on RNA from human colon cancer cell lines and matched normal and tumor colon cancer tissues from human patients, revealing three novel targets (rat brain serine protease2, AMP deaminase 3, and cartilage link protein 1). CONCLUSION: Following MEK-activation, many tumor-associated genes were found to have significantly altered expression levels. However, we identified three genes that were differentially expressed in caMEK cells and human colorectal cancers, which have not been previously linked to cellular transformation or tumorogenesis.

Animals↗

PubMed2003

Gene expression profiling of Caco-2 BBe cells suggests a role for specific signaling pathways during intestinal differentiation.

We examined the pattern of gene expression resulting from spontaneous differentiation of Caco-2 BBe cells to gain insight into the molecular changes necessary for enterocyte differentiation. RNA was prepared from cells harvested at three cell stages: proliferating (50% confluent, 2 days in culture), postproliferative nondifferentiated (8 days), and differentiated (15 days). Gene expression profiles were determined using Affymetrix Human Genome U95A GeneChips. Differentially expressed genes were identified following statistical analysis (i.e., ANOVA, bootstrapping adjustments to P values, false detection rate criterion). We identified 1,150 unique genes as differentially expressed; expression of 48.6% fell and 46% increased from 2 to 15 days, while 5.4% had expression that either peaked or dipped at 8 days. Genes expressed during differentiation included several small-intestine-specific genes involved in nutrient transport/metabolism, e.g., DCT1, hephaestin, folate receptor 1, sucrase-isomaltase, and apolipoproteins CI, CIII, B100, H, and M, indicating that this colonic adenocarcinoma cell line has a hybrid colonocyte/enterocyte phenotype. Patterns of gene expression based upon functional classification suggest a role for cell-cell/cell-matrix interactions, suppression of Wnt signaling, and activation of TGFbeta and phosphatidylinositol 3-kinase pathways during enterocyte differentiation.

Caco-2 Cells↗

PubMed2004

Hunting drug targets by systems-level modeling of gene expression profiles.

Structural learning of Bayesian networks applied to sets of genome-wide expression patterns has been recently discovered as a potentially useful tool for the systems-level statistical description of gene interactions. We train and analyze Bayesian networks with the goal of inferring biological aspects of gene function. Our two-component approach focuses on supporting the drug discovery process by identifying genes with central roles for the network operation, which could act as drug targets. The first component, referred to as scale-free analysis, uses topological measures of the network-related to a high-traffic load of genes-as estimators for their functional importance. The second component, referred to as generative inverse modeling, is a method of estimating the effect of a simulated drug treatment or mutation on the global state of the network, as measured in the expression profile. We show for a dataset from acute lymphoblastic leukemia patients that both approaches are suitable for finding genes with central cellular functions. In addition, generative inverse modeling correctly identifies a known oncogene in a purely data-driven way.

Algorithms↗