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Results for “expression profiling”

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PubMed2001

Expression profiles of endometrial leukemia inhibitory factor, transforming growth factor beta2 (TGFbeta2), and TGFbeta2 receptor in infertile bonnet monkeys.

The expression profiles of leukemia inhibitory factor (LIF), transforming growth factor beta2 (TGFbeta2), and transforming growth factor beta2 receptor (TGFbeta2R) were analyzed during the peri-implantation period in regularly menstruating, fertile bonnet monkeys and in animals in which endometrial nonreceptivity was induced by administering an antiprogestin, onapristone. Based on our previous experiences, a dose of 2.5 or 5 mg of onapristone was administered s.c. every third day during the menstrual cycle, because these dosages impair endometrial development without upsetting the normal gonadal endocrine profiles. Endometrial biopsy specimens were collected during the proliferative phase (estradiol levels about 200 pg/ml, n = 5) and peri-implantation period (Day 8 after midcycle peak in estradiol levels, n = 5) from normal ovulatory animals and during the peri-implantation period from onapristone-treated animals (n = 10). The biopsy specimens were processed to determine the expression patterns of LIF, TGFbeta2, and TGFbeta2R by immunohistochemical and reverse transcription-polymerase chain reaction (RT-PCR) methods. Levels of both protein and mRNA for LIF, TGFbeta2, and TGFbeta2R (analyzed by immunohistochemistry and RT-PCR, respectively) were greater in the endometrial samples collected during the peri-implantation period compared to samples collected during the proliferative phase in control animals. Treatment with either of the two doses (2.5 or 5 mg) of onapristone caused a significant (P < 0.05) down-regulation in the expression of LIF in the peri-implantation endometria. The endometrial expressions of TGFbeta2 and TGFbeta2R mRNAs were reduced significantly in animals treated with 5 mg of onapristone, but not in those treated with the lower dose. However, immunoreactive TGFbeta2 and TGFbeta2R proteins were significantly (P < 0.05) down-regulated in the endometrial samples from both the 2.5- and 5-mg-treated groups. The alterations observed in the expression patterns of LIF, TGFbeta2, and TGFbeta2R were specific, because the expression levels of epidermal growth factor receptor remained unaffected in the endometria from the treated groups. The present study demonstrates derangement in the expression profiles of LIF, TGFbeta2, and TGFbeta2R during the peri-implantation period in infertile bonnet monkeys. It may be hypothesized that TGFbeta2 function is one of the early steps in the regulation of the progesterone-driven cascade of events leading to endometrial receptivity, and that any aberration in this step may adversely affect the subsequent molecular events (i.e., expression of LIF). These data also suggest that potential aberrations in the functional network of locally produced cytokines and growth factors even may occur in an endometrium exposed to the optimal peripheral hormonal levels.

Animals↗

PubMed2004

Unique gene expression profiles of heart allograft rejection in the interferon regulatory factor-1-deficient mouse.

Interferon regulatory factor-1 (IRF1) is a transcription factor for many genes involved in innate and adaptive immune responses. By using DNA array technology, we have previously demonstrated that IRF1 is significantly upregulated during acute rejection in rat heart allografts and is restored to isograft levels when recipients are treated with the immunosuppressants tacrolimus or cyclosporin A (CsA). To understand the precise role of IRF1 in transplant rejection, we investigated the rejection responses of mice completely deficient of IRF1 protein. Heterotopic heart transplantations were performed using C57BL/6J wild-type (WT B6) and IRF1-deficient (IRF1-/-) mice as recipients, and C3H mice as donors. Graft survival was determined by abdominal palpation and rejection was confirmed by histology. On day 6 after transplantation, isografts and allografts were harvested and subjected to gene expression analysis by a commercial nylon array and by real-time RT-PCR. Median survival time of heart allografts was 8 days in the WT B6 mice and 10 days in the IRF1-/- mice. The gene expression profiles of allografts from the WT B6 and IRF1-/- recipients were nearly identical to each other and very different from the profile of the isograft control. Both WT B6 and IRF1-/- profiles showed 13 genes upregulated (IFN-gamma, MCP-2, MIP-1alpha, MIP-1beta, CCR5, MIG, IP-10 and others) and one gene downregulated (SDF2) among the 76 genes detectable on the array. In more detailed analyses, distinct cytokine and chemokine gene expression profiles were identified in the allografts from the WT B6 and IRF1-/- recipients. Whereas IL-4, IL-6, IL-13, MCP-1, MCP-3, and MPIF-2 were upregulated, RANTES, IL-2Rgamma and gp130 were downregulated in allografts from the IRF1-/- recipients when compared to the WT B6 control. Although the inactivation of the IRF1 gene did not sufficiently prevent acute allograft rejection in this model, a unique cytokine and chemokine gene expression profile was found in the absence of IRF1.

Animals↗

PubMed2006

Expression profiling correlates with treatment response in women with advanced serous epithelial ovarian cancer.

The majority of epithelial ovarian carcinomas are of serous subtype, with most women presenting at an advanced stage. Approximately 70% respond to initial chemotherapy but eventually relapse. We aimed to find markers of treatment response that might be suitable for routine use, using the gene expression profile of tumor tissue. Thirty one women with histologically-confirmed late-stage serous ovarian cancer were classified into 3 groups based on response to treatment (nonresponders, responders with relapse less than 12 months and responders with no relapse within 12 months). Gene expression profiles of these specimens were analyzed with respect to treatment response and survival (minimum 36 months follow-up). Patients' clinical features did not correlate with prognosis, or with specific gene expression patterns of their tumors. However women who did not respond to treatment could be distinguished from those who responded with no relapse within 12 months based on 34 gene transcripts (p < 0.02). Poor prognosis was associated with high expression of inhibitor of differentiation-2 (ID2) (p = 0.001). High expression of decorin (DCN) and ID2 together was strongly associated with reduced survival (p = 0.003), with an estimated 7-fold increased risk of dying (95% CI 1.9-29.6; 14 months survival) compared with low expression (44 months). Immunohistochemical analysis revealed both nuclear and cytoplasmic distribution of ID2 in ovarian tumors. High percentage of nuclear staining was associated with poor survival, although not statistically significantly. In conclusion, elevated expression of ID2 and DCN was significantly associated with poor prognosis in a homogeneous group of ovarian cancer patients for whom survival could not be predicted from clinical factors.

Antineoplastic Agents↗

PubMedDate not supplied

Expression profiles of 50 xenobiotic transporter genes in humans and pre-clinical species: a resource for investigations into drug disposition.

Carrier-mediated transporters play a critical role in xenobiotic disposition and transporter research is complicated by species differences and their selective tissue expression. The purpose of this study was to generate a comprehensive data set of xenobiotic transporter gene expression profiles in humans and the pre-clinical species mouse, rat, beagle dog and cynomolgus monkey. mRNA expression profiles of 50 genes from the ABC, SLC and SLCO transporter superfamilies were examined in 40 human tissues by microarray analyses. Transporter genes that were identified as enriched in the liver or kidney, or that were selected for their known roles in xenobiotic disposition, were then compared in 22 tissues across the five species. Finally, as clinical variability in drug response and adverse reactions may be the result of variability in transporter gene expression, variability in the expression of selected transporter genes in 75 human liver donors were examined and compared with the highly variable drug metabolizing enzyme CYP3A4.

Animals↗

PubMed2005

Gene expression profiling of microsatellite unstable and microsatellite stable endometrial cancers indicates distinct pathways of aberrant signaling.

Microsatellite instability (MSI) is a molecular phenotype present in approximately 25% of endometrial cancers. We examined the global gene expression profiles of early-stage endometrioid endometrial cancers with and without the MSI phenotype to test the hypothesis that MSI phenotype may determine a unique molecular signature among otherwise similar cancers. Unsupervised principal component analysis of the expression data from these cases indicated two distinct groupings of cancers based on MSI phenotype. A relatively small number of array features (392) at high statistical value (P < 0.001) were identified that drive the instability signature in these cancers; 109 of these transcripts differed by at least 2-fold. These data identify distinct gene expression profiles for MSI and microsatellite stable (MSS) cancers, which suggest that cancers with MSI develop in part by different mechanisms from their similar stable counterparts. In particular, we found evidence that two members of the secreted frizzled related protein family (SFRP1 and SFRP4) were more frequently down-regulated in MSI cancers as compared with MSS cancers. Down-regulation was accompanied by promoter hypermethylation for SFRP1. SFRP1 was hypermethylated in 8 of 12 MSI cancers whereas only 3 of 16 MSS cancers were methylated. The WNT target fibroblast growth factor 18 was found to be up-regulated in MSI cancers. These data classify histologically similar endometrioid endometrial cancers into two distinct groupings with implications affecting therapy and prevention.

Carcinoma, Endometrioid↗

PubMed2004

Characterization of liver-cirrhosis nodules by analysis of gene-expression profiles and patterns of allelic loss.

To disclose genetic mechanisms involved in development or progression of hepatocellular carcinoma (HCC), we used a genome-wide cDNA microarray consisting of 8,448 genes to compare gene-expression profiles among 12 liver-cirrhosis nodules (LCNs) and five specimens of HCC excised from a single patient and carefully prepared by laser-capture microdissection (LCM). The expression patterns enabled us to identify 72 genes that were frequently upregulated and 57 that were downregulated specifically in the LCN specimens as compared to the HCCs. We also documented upregulation of 31 genes and downregulation of seven others in both HCC and LCN tissues. Several types of intracellular kinase, including receptor-type kinase, were upregulated in LCNs. Expression patterns of HCCs and LCNs generally represented two genetically distinct groups when subjected to a hierarchical clustering analysis, although expression profiles of two of the LCNs resembled the HCC pattern. Analysis of allelic losses at microsatellite loci revealed that LCNs showed frequent loss of heterozygosity (LOH) (33%) in chromosomal regions 6q and 22q; over half of the LCNs had lost an allele for at least one of the 28 loci examined. The presence of early genetic changes among LCNs, with additional genetic changes occurring during formation of HCCs, suggests that hepatocellular carcinogenesis follows the multistep model established for colon cancers and that some LCNs may be precancerous lesions.

Carcinoma, Hepatocellular↗

PubMed2005

[Gene expression profiles in early stage of BALB/c 3T3 cells' transformation promoted with 12-O-tetradecanoylphorbol-13-acetate].

OBJECTIVE: To elucidate the potential molecular mechanism responsible for the early time of tumor promotion, gene expression profile was studied in the transformed BALB/c 3T3 cells induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). METHODS: The two-stage cell transformation model was established by using the initiator of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and promoter of TPA. Cell proliferation was measured by trypan blue staining and cell cycle analysis was carried out by flow cytometry assay. A cDNA microarray representing 1 152 genes was used to investigate the gene expression profiles of BALB/c 3T3 cells exposed to TPA at 4 h and 24 h respectively. RESULTS: TPA could effectively inhibit cell proliferation and induce the G1 and S cell cycle arrested in the early time. Moreover 19 genes were found differentially expressed at least twofold in the TPA treated cells as compared with the control cells, 9 of them were upregulated and 10 downregulated. Most of the differentially expressed genes were involved in cell proliferation, differentiation or apoptosis, and related to ras or p53 signal transduction pathway. CONCLUSION: TPA could influence the transcriptional expression of some genes related to cell cycle modulation and ultimately result in the cell growth arrest.

Animals↗

PubMed2003

Dynamic and coordinated expression profile of dbl-family guanine nucleotide exchange factors in the developing mouse brain.

Dbl-family guanine nucleotide exchange factors (Dbl-GEFs) act as activators of Rho-like small G proteins such as Rac1, Cdc42 and RhoA. Recently, some GEFs have been suggested to play important roles in the development of the nervous system. Here, we report a comprehensive expression profile analysis of 20 Dbl-GEFs that have yet to be well investigated. Northern analyses of murine mRNAs from brains of E13, E17, P7 and adult mice revealed expression of 18 out of 20 GEFs in some or all stages. In addition, we found that three human GEFs were highly expressed in the brain. Examination of the spatial expression patterns of five GEFs in embryos or neonatal brain by in situ hybridization revealed distinct patterns for each GEF. Our study reveals the dynamic and coordinated expression profiles of the Dbl-GEFs and provides a basic framework for understanding the function of GEFs in neural development.

Amino Acid Sequence↗

PubMed2006

Gene expression profile of the adult human retinal ganglion cell layer.

PURPOSE: Pathophysiological events in the retinal ganglion cell layer (GCL) are a prominent feature of several optic neuropathies including glaucoma. The purpose of this study was to identify and catalog genes whose expression in the human retina is restricted to the GCL. METHODS: Laser capture microdissection (LCM) technology was used to isolate tissue from the perimacular retina of three human donors without retinal or optic nerve disease. RNA was isolated from the (1) retinal GCL and (2) the inner and outer nuclear layers of the same retina, and the gene expression profiles of both fractions were determined using Affymetrix Hu133Plus 2.0 GeneChips. Data were analyzed to identify those genes whose expression is substantially more prevalent in the GCL when compared to the outer retinal layers. Differential expression of selected genes was confirmed by real-time PCR and immunohistochemistry. RESULTS: The results show that mRNA levels of previously described ganglion cell markers, e.g. the neurofilament genes (NEFH, NEF3, or NEFL) and the Brn3a transcription factor (POU4F1), were highly enriched in the isolated GCL fraction. In contrast, transcripts for genes associated with phototransduction (RHO), photoreceptor development (NR2E3), or interphotoreceptor matrix constituents (IMPG1) were nearly absent from the GCL fraction. Using bioinformatics approaches over 80 genes were identified whose expression in the human retina appears to be limited to the GCL. CONCLUSIONS: We have successfully used LCM technology to generate gene expression profiles of highly enriched GCL fractions of the normal human retina. These data not only provide clues to the normal function of retinal ganglion cells but also serve as a resource in the development of ganglion cell specific markers or transfection vectors, and the identification of candidate genes for hereditary forms of glaucoma.

Aged↗

PubMed2006

Gene array expression profiling in acne lesions reveals marked upregulation of genes involved in inflammation and matrix remodeling.

The pathogenesis of acne has been linked to multiple factors such as increased sebum production, inflammation, follicular hyperkeratinization, and the action of Propionibacterium acnes within the follicle. In an attempt to understand the specific genes involved in inflammatory acne, we performed gene expression profiling in acne patients. Skin biopsies were obtained from an inflammatory papule and from normal skin in six patients with acne. Biopsies were also taken from normal skin of six subjects without acne. Gene array expression profiling was conducted using Affymetrix HG-U133A 2.0 arrays comparing lesional to nonlesional skin in acne patients and comparing nonlesional skin from acne patients to skin from normal subjects. Within the acne patients, 211 genes are upregulated in lesional skin compared to nonlesional skin. A significant proportion of these genes are involved in pathways that regulate inflammation and extracellular matrix remodeling, and they include matrix metalloproteinases 1 and 3, IL-8, human beta-defensin 4, and granzyme B. These data indicate a prominent role of matrix metalloproteinases, inflammatory cytokines, and antimicrobial peptides in acne lesions. These studies are the first describing the comprehensive changes in gene expression in inflammatory acne lesions and are valuable in identifying potential therapeutic targets in inflammatory acne.

Acne Vulgaris↗

PubMed2006

Gene expression profiling on lung cancer outcome prediction: present clinical value and future premise.

DNA microarray has been widely used in cancer research to better predict clinical outcomes and potentially improve patient management. The new approach provides accurate tumor classification and outcome predictions, such as tumor stage, metastatic status, and patient survival, and offers some hope for individualized medicine. However, growing evidence suggests that gene-based prediction is not stable and little is known about the prediction power of gene expression profiles compared with well-known clinical and pathologic predictors. This review summarized up-to-date publications in microarray-based lung cancer clinical outcome prediction and conducted secondary analyses for those with sufficient sample sizes and associated clinical information. Among the most commonly used analytic approaches, unsupervised clustering mainly recaptures tumor histology and provides variable degrees of prediction for tumor stage, lymph node status, or survival. Overall, most studies lack an independent validation. Supervised learning and testing generally offer a better prediction. Noted is that when conventional predictors of age, gender, stage, cell type, and tumor grade are considered collectively, the predictive advantage of the gene expression profiles diminishes. We conclude that outcome prediction from gene expression signatures selected by current analytic approaches can be mostly explained by well-known conventional predictors, particularly histologic subtype and grade of differentiation. A strategy for establishing independent or more accurate signatures is commented.

Cell Differentiation↗

PubMed2003

MAPPFinder: using Gene Ontology and GenMAPP to create a global gene-expression profile from microarray data.

MAPPFinder is a tool that creates a global gene-expression profile across all areas of biology by integrating the annotations of the Gene Ontology (GO) Project with the free software package GenMAPP http://www.GenMAPP.org. The results are displayed in a searchable browser, allowing the user to rapidly identify GO terms with over-represented numbers of gene-expression changes. Clicking on GO terms generates GenMAPP graphical files where gene relationships can be explored, annotated, and files can be freely exchanged.

Animals↗

PubMed2003

Tobacco mosaic virus induced alterations in the gene expression profile of Arabidopsis thaliana.

In this study, mRNA profiles generated from cDNA microarrays were used to identify gene expression changes in Arabidopsis thaliana ecotype Shahdara infected with Tobacco mosaic virus (TMV). Shahdara is a susceptible TMV host, permitting rapid accumulations of virus in both inoculated and systemic tissues, accompanied by defined disease symptoms that include stunting, necrosis, and leaf curling. Gene expression profiles were monitored in whole tissues of inoculated leaves at four days postinoculation (dpi) and in systemically infected leaves at 14 dpi. Microarrays contained cDNAs representing between 8,000 and 10,000 Arabidopsis genes. Expression analysis identified 68 genes that displayed significant and consistent changes in expression levels, either up or down, in either TMV inoculated or systemically infected tissues, or both. Identified TMV-responsive genes encode a diverse array of functional proteins that include transcription factors, antioxidants, metabolic enzymes, and transporters. Thus, the TMV infection process has a significant impact on a wide array of cellular processes that likely reflect the biochemical and physiological changes involved in the development of this disease syndrome.

Arabidopsis↗

PubMed2006

Whole genome expression profiling of glucose-dependent insulinotropic peptide (GIP)- and adrenocorticotropin-dependent adrenal hyperplasias reveals novel targets for the study of GIP-dependent Cushing's syndrome.

CONTEXT: The mechanisms responsible for the ectopic adrenal expression of glucose-dependent insulinotropic peptide (GIP) receptor (GIPR) in GIP-dependent Cushing's syndrome (CS) are unknown. Chronic adrenal stimulation by ACTH in Cushing's disease or GIP in GIP-dependent ACTH-independent macronodular adrenal hyperplasia both lead to the induction of genes implicated in adrenal proliferation and steroidogenesis. OBJECTIVE: The objective of the study was to identify genes differentially expressed specifically in GIP-dependent CS that could be implicated in the ectopic expression of GIPR. METHODS: We used the Affymetrix U133 plus 2.0 microarray oligochips to compare the whole genome expression profile of adrenal tissues from five cases of GIP-dependent bilateral ACTH-independent macronodular adrenal hyperplasia with CS, one case of GIP-dependent unilateral adenoma with CS, five cases of ACTH-dependent hyperplasias, and a pool of adrenals from 62 normal individuals. RESULTS: After data normalization and statistical filtering, 723 genes with differential expression were identified, including 461 genes or sequences with a known functional implication, classified in eight dominant functional classes. Specific findings include repression of perilipin, the overexpression of 13 G protein-coupled receptors, and the potential involvement of Rho-GTPases. We also isolated 94 probe sets potentially linked to the formation of GIP-dependent nodules adjacent to the diffuse hyperplasia. These included probe sets related to the linker histone H1 and repression of RXRa and CCND2. The expression profiles for eight genes were confirmed by real-time RT-PCR. CONCLUSION: This study identified an extensive series of potentially novel target candidate genes that could be implicated in the molecular mechanisms of ectopic expression of the GIPR as well as in the multistep progression of GIP-dependent CS.

Adolescent↗

PubMed2003

The Arabidopsis SKP1-like genes present a spectrum of expression profiles.

The yeast Skp1 protein is a component of the SCF complex, an E3 enzyme involved in the specific protein degradation pathway via ubiquitination. Skp1 binds to F-box proteins to trigger specific recognition of proteins targeted for degradation. SKP1-like genes have been found in a variety of eukaryotes including yeast, man, Caenorhabditis elegans and Arabidopsis thaliana. The Arabidopsis genome contains 20 SKP1-like genes called ASK (for Arabidopsis SKP1-like), among which only ASK1 has been characterized in detail. The analysis of the expression pattern of the ASK genes in Arabidopsis should provide key information for the understanding of the biological role of this family in protein degradation and in different cellular mechanisms. In this paper, we describe the expression profiles of 19 ASK promoter-GUS fusions in stable transformants of Arabidopsis, with a special emphasis on floral organ development. Four ASK promoters did not show any detectable expression in either inflorescences or seedlings. Our results on the ASK1 expression profile are consistent with previous reports. Several ASK promoters show clear tissue-specific expression (for instance in the connective of anthers or in the embryo). We also found that almost half (9/19) of ASK promoters direct a post-meiotic expression in the male gametophyte. Tight regulation of the expression of this gene family indicates a crucial role of the ubiquitin degradation pathway during development, particularly during male gametophyte development.

Amino Acid Sequence↗

PubMed2004

PCR-array gene expression profiling of hepatocellular carcinoma.

Many trials using DNA microarrays have been reported for various human malignancies, but an efficient molecular diagnostic system has yet to be established. Here, we adopted a high throughput quantitative PCR-array system based on adaptor-tagged competitive PCR (ATAC-PCR), as a novel technique for gene expression profiling of hepatocellular carcinoma (HCC). This PCR-array contained 3,072 genes derived from three different cDNA libraries, including 298 additional known genes suspected to be involved in hepatocarcinogenesis. Using this PCR-array with 20 pairs of liver tissues (20 HCC, 20 surrounding nontumor liver), we identified a total of 117 genes differing in expression levels in the two liver tissues. Hierarchical clustering analysis and principal component analysis with these genes revealed distinct gene expression patterns in the HBV-positive group and the HCV-positive groups. Among 117 genes, only 7 (GPAA1, TMEM9, FACL4, ADFP, MAWBP, PACE4, FOS) were common to both groups. In conclusion, this PCR-array analysis with an appropriate set of genes is considered useful for gene expression profiling of HCC, and we identified some genes which may play a common key role in hepatocarcinogenesis.

Aged↗

PubMed2003

On parametric empirical Bayes methods for comparing multiple groups using replicated gene expression profiles.

DNA microarrays provide for unprecedented large-scale views of gene expression and, as a result, have emerged as a fundamental measurement tool in the study of diverse biological systems. Statistical questions abound, but many traditional data analytic approaches do not apply, in large part because thousands of individual genes are measured with relatively little replication. Empirical Bayes methods provide a natural approach to microarray data analysis because they can significantly reduce the dimensionality of an inference problem while compensating for relatively few replicates by using information across the array. We propose a general empirical Bayes modelling approach which allows for replicate expression profiles in multiple conditions. The hierarchical mixture model accounts for differences among genes in their average expression levels, differential expression for a given gene among cell types, and measurement fluctuations. Two distinct parameterizations are considered: a model based on Gamma distributed measurements and one based on log-normally distributed measurements. False discovery rate and related operating characteristics of the methodology are assessed in a simulation study. We also show how the posterior odds of differential expression in one version of the model is related to the ratio of the arithmetic mean to the geometric mean of the two sample means. The methodology is used in a study of mammary cancer in the rat, where four distinct patterns of expression are possible.

Animals↗

PubMed2005

[Changes of gene expression profiles in CCl4 injured liver of mice].

AIM: To study the gene expression profiles between the CCl4 injured liver and normal liver in mice, and to screen the differentially expressed genes that relate to liver injury by CCl4 on a large scale using cDNA microarrays. METHODS: Male Kunming strain mice were divided into two groups: one was control group and another was CCl4 injured liver group that was given 0.1% CCI4 oil solution ip at dose of 10 mL x kg(-1) every three days, totally for ten times. Then mRNA in livers of the two groups of mice was extracted, separately, and reversely transcribed to cDNA with the incorporation of different fluorescent-labeled dUTP as the hybridization probes. The mixed probes were hybridized to the cDNA microarrays. The fluorescent signal values were acquired by scanner and analyzed with statistical software. RESULTS: Among the 14 100 target genes, 379 genes were differentially expressed, in which 163 genes were up-regulated and the other 216 genes were down-regulated. They are closely related to a range of biological functions. CONCLUSION: Using the cDNA microarray and experimental animal modeling technique, the differentially expressed genes of CCl4 injured liver in mice on a large scale could be studied. It is useful for further investigation of the injury mechanism of CCl4.

Alanine Transaminase↗