Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • GENES  (8)
  • 1
    Keywords: CELLS ; EXPRESSION ; Germany ; SYSTEMS ; GENE ; GENE-EXPRESSION ; GENES ; microarray ; SACCHAROMYCES-CEREVISIAE ; METABOLISM ; COMPLEX ; COMPLEXES ; SEQUENCE ; METABOLITES ; gene expression ; ESCHERICHIA-COLI ; DATABASE ; OXYGEN ; CLUSTER ; MATRIX ; SYNTHETASE ; EXTRACTION ; LEVEL ; ENZYME ; TECHNOLOGY ; EXPRESSION PATTERNS ; CHAIN AMINO-ACIDS ; K-12
    Abstract: Background: Microarray technology produces gene expression data on a genomic scale for an endless variety of organisms and conditions. However, this vast amount of information needs to be extracted in a reasonable way and funneled into manageable and functionally meaningful patterns. Genes may be reasonably combined using knowledge about their interaction behaviour. On a proteomic level, biochemical research has elucidated an increasingly complete image of the metabolic architecture, especially for less complex organisms like the well studied bacterium Escherichia coli. Results: We sought to discover central components of the metabolic network, regulated by the expression of associated genes under changing conditions. We mapped gene expression data from E. coli under aerobic and anaerobic conditions onto the enzymatic reaction nodes of its metabolic network. An adjacency matrix of the metabolites was created from this graph. A consecutive ones clustering method was used to obtain network clusters in the matrix. The wavelet method was applied on the adjacency matrices of these clusters to collect features for the classifier. With a feature extraction method the most discriminating features were selected. We yielded network sub-graphs from these top ranking features representing formate fermentation, in good agreement with the anaerobic response of heterofermentative bacteria. Furthermore, we found a switch in the starting point for NAD biosynthesis, and an adaptation of the l-aspartate metabolism, in accordance with its higher abundance under anaerobic conditions. Conclusion: We developed and tested a novel method, based on a combination of rationally chosen machine learning methods, to analyse gene expression data on the basis of interaction data, using a metabolic network of enzymes. As a case study, we applied our method to E. coli under oxygen deprived conditions and extracted physiologically relevant patterns that represent an adaptation of the cells to changing environmental conditions. In general, our concept may be transferred to network analyses on biological interaction data, when data for two comparable states of the associated nodes are made available
    Type of Publication: Journal article published
    PubMed ID: 16524469
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    Keywords: CANCER ; PATHWAY ; GENES ; ACTIVATION ; MUTATIONS ; SUBGROUPS ; LANDSCAPE ; TETRAPLOID TUMOR-CELLS ; TBR1
    Abstract: Medulloblastoma is an aggressively growing tumour, arising in the cerebellum or medulla/brain stem. It is the most common malignant brain tumour in children, and shows tremendous biological and clinical heterogeneity. Despite recent treatment advances, approximately 40% of children experience tumour recurrence, and 30% will die from their disease. Those who survive often have a significantly reduced quality of life. Four tumour subgroups with distinct clinical, biological and genetic profiles are currently identified. WNT tumours, showing activated wingless pathway signalling, carry a favourable prognosis under current treatment regimens. SHH tumours show hedgehog pathway activation, and have an intermediate prognosis. Group 3 and 4 tumours are molecularly less well characterized, and also present the greatest clinical challenges. The full repertoire of genetic events driving this distinction, however, remains unclear. Here we describe an integrative deep-sequencing analysis of 125 tumour-normal pairs, conducted as part of the International Cancer Genome Consortium (ICGC) PedBrain Tumor Project. Tetraploidy was identified as a frequent early event in Group 3 and 4 tumours, and a positive correlation between patient age and mutation rate was observed. Several recurrent mutations were identified, both in known medulloblastoma-related genes (CTNNB1, PTCH1, MLL2, SMARCA4) and in genes not previously linked to this tumour (DDX3X, CTDNEP1, KDM6A, TBR1), often in subgroup-specific patterns. RNA sequencing confirmed these alterations, and revealed the expression of what are, to our knowledge, the first medulloblastoma fusion genes identified. Chromatin modifiers were frequently altered across all subgroups. These findings enhance our understanding of the genomic complexity and heterogeneity underlying medulloblastoma, and provide several potential targets for new therapeutics, especially for Group 3 and 4 patients.
    Type of Publication: Journal article published
    PubMed ID: 22832583
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    Keywords: CANCER ; CANCER CELLS ; CELLS ; EXPRESSION ; GROWTH ; INVASION ; tumor ; TUMOR-CELLS ; CELL ; Germany ; human ; SITE ; SITES ; GENE ; GENES ; transcription ; COMPONENTS ; MOLECULES ; TISSUE ; MECHANISM ; FAMILY ; TRANSCRIPTION FACTOR ; IMPACT ; CARCINOGENESIS ; INDUCTION ; mechanisms ; BINDING ; SIGNAL ; MOLECULE ; ALPHA ; cytokines ; TARGET ; DELETION ; CHROMATIN ; PROMOTER ; MEMBRANE ; PROMOTERS ; MUTATION ; inactivation ; DERIVATIVES ; REGION ; CANCER-CELLS ; REGIONS ; MUTATIONS ; BETA ; SUPERFAMILY ; GROWTH-FACTOR-BETA ; TRANSCRIPTIONAL REGULATION ; GAMMA-2 CHAIN ; CYTOKINE ; molecular ; ONCOLOGY ; FAMILIES ; TUMOR SUPPRESSION ; TUMOR-SUPPRESSOR ; basement membrane ; TRANSFECTION ; TGF-BETA ; interaction ; MOLECULAR-MECHANISMS ; methods ; SUPPRESSOR ; TGF beta ; SIGNALS ; COLON-CARCINOMA CELLS ; BARRIER ; ENGLAND ; UPSTREAM ; response ; synthesis ; Smad4 ; SUPPRESSOR E-CADHERIN ; chromatin immunoprecipitation ; tumor suppressor ; FUNCTIONAL INACTIVATION ; BINDING SITE ; ACTIVATOR PROTEIN-1 ; AP-1 COMPLEX
    Abstract: Background: Functional inactivation of the tumor suppressor Smad4 in colorectal and pancreatic carcinogenesis occurs coincident with the transition to invasive growth. Breaking the basement membrane ( BM) barrier, a prerequisite for invasive growth, can be due to tumor induced proteolytic tissue remodeling or to reduced synthesis of BM molecules by incipient tumor cells. Laminin-332 (laminin-5), a heterotrimeric BM component composed of alpha 3-, beta 3- and gamma 2-chains, has recently been identified as a target structure of Smad4 and represents the first example for expression control of an essential BM component by a tumor and invasion suppressor. Biochemically Smad4 is a transmitter of signals of the TGF beta superfamily of cytokines. We have reported previously, that Smad4 functions as a positive transcriptional regulator of constitutive and of TGF beta-induced transcription of all three genes encoding Laminin-332, LAMA3, LAMB3 and LAMC2. Methods: Promoter-reporter constructs harboring 4 kb upstream regions, each of the three genes encoding Laminin-322 as well as deletion and mutations constructs were established. Promoter activities and TGF beta induction were assayed through transient transfections in Smad4-negative human cancer cells and their stable Smad4-positive derivatives. Functionally relevant binding sites were subsequently confirmed through chromatin immunoprecipitation. Results: Herein, we report that Smad4 mediates transcriptional regulation through three different mechanisms, namely through Smad4 binding to a functional SBE site exclusively in the LAMA3 promoter, Smad4 binding to AP1 (and Sp1) sites presumably via interaction with AP1 family components and lastly a Smad4 impact on transcription of AP1 factors. Whereas Smad4 is essential for positive regulation of all three genes, the molecular mechanisms are significantly divergent between the LAMA3 promoter as compared to the LAMB3 and LAMC2 promoters. Conclusion: We hypothesize that this divergence in modular regulation of the three promoters may lay the ground for uncoupled regulation of Laminin-332 in Smad4-deficient tumor cells in response to stromally expressed cytokines acting on budding tumor cells
    Type of Publication: Journal article published
    PubMed ID: 18664273
    Signatur Availability
    BibTip Others were also interested in ...
  • 4
    Keywords: EXPRESSION ; SURVIVAL ; carcinoma ; CELL ; Germany ; CLASSIFICATION ; DIAGNOSIS ; FOLLOW-UP ; RISK ; SITE ; SITES ; GENES ; PROTEIN ; TISSUE ; TUMORS ; PATIENT ; IMPACT ; IDENTIFICATION ; REGION ; RECURRENCE ; REGIONS ; SQUAMOUS-CELL CARCINOMA ; HEAD ; NECK ; pathology ; relapse ; PROTEOMICS ; PROTEOMIC ANALYSIS ; NECK-CANCER ; CELL CARCINOMA ; ONCOLOGY ; HNSCC ; PROFILES ; prospective ; SELDI-TOF-MS ; SQUAMOUS-CELL ; PROFILE ; field cancerization ; tumours ; HEAD-AND-NECK ; Follow up ; proteomic ; biomarker protein profiles ; CHROMOSOME-17 ; ORAL EPITHELIAL DYSPLASIA ; pharynx and oesophagus carcinoma
    Abstract: 'Field cancerization' in head and neck squamous cell carcinoma (HNSCC) is poorly understood and it may extend from the pharynx into the oesophagus. Both local recurrences and second primary carcinomas/second field tumours may originate from field cancerization. Our prospective pilot study aimed at the identification of patients suffering from field cancerization on the basis of mucosal protein profiles. Five mucosal biopsies from the oropharynx, hypopharynx and from three regions of the oesophagus were taken from 24 patients. Protein profiles were generated from the mucosal biopsies. After classifier learning, using the profiles of the patients without tumour diagnosis (n = 9), we were able to discriminate between the different mucosal sites and between healthy mucosa and HNSCC using tumour and healthy tissue samples. Mucosal biopsies of tumour patients (n = 15) revealed changes in the protein profiles similar to those in the tumours. During 42 months median follow-up, six tumour patients experienced local recurrences and second field tumours, of which three occurred in the oesophagus. In all six cases, tumour relapse was correctly predicted by altered mucosal protein profiles (p = 0.007, Fisher's exact test, two-tailed). Consequently, molecular field cancerization had a strong impact on progression-free survival (p = 0.007, log-rank test). Protein profiles of small diagnostic biopsies hold great promise to improve personalized risk assessment in HNSCC. Larger studies are needed to further substantiate these findings. Copyright (C) 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd
    Type of Publication: Journal article published
    PubMed ID: 20593486
    Signatur Availability
    BibTip Others were also interested in ...
  • 5
    Keywords: CANCER ; CANCER CELLS ; CELLS ; EXPRESSION ; GROWTH ; IN-VITRO ; tumor ; carcinoma ; CELL ; Germany ; human ; IN-VIVO ; MODEL ; VITRO ; VIVO ; SYSTEM ; GENE ; GENE-EXPRESSION ; GENES ; cell line ; TRANSDUCTION ; RESPONSES ; IMPACT ; INDUCTION ; tumour ; DOWN-REGULATION ; SUPPRESSION ; SIGNAL ; cytokines ; TARGET ; gene expression ; resistance ; CARCINOMA CELLS ; colorectal cancer ; COLORECTAL-CANCER ; cervical cancer ; CERVICAL-CANCER ; CELL-LINE ; LINE ; SIGNALING PATHWAY ; CANCER-CELLS ; COLORECTAL CANCERS ; EXTRACELLULAR-MATRIX ; CARCINOMA-CELLS ; SUPERFAMILY ; CERVICAL-CARCINOMA ; cervical carcinoma ; GROWTH-FACTOR-BETA ; TARGETS ; C-MYC ; OVEREXPRESSION ; pancreatic carcinoma ; HIGH-LEVEL ; CELL-GROWTH ; CYTOKINE ; MATRIX ; ONCOLOGY ; TUMOR SUPPRESSION ; LIGHT ; extracellular matrix ; RESTORATION ; regulation ; TGF-BETA ; interaction ; LEVEL ; TARGET GENES ; methods ; pancreatic ; SUPPRESSOR ; EVENTS ; tumour suppressor ; function ; LOSSES ; CANCERS ; in vivo ; SIGNALS ; carcinogenic ; COLON-CARCINOMA CELLS ; ENGLAND ; PREDICT ; colorectal ; NOV ; evidence ; cell growth ; BETAIG-H3 GENE ; BRONCHIAL EPITHELIAL-CELLS ; Smad4 ; STABLE RNA INTERFERENCE ; SUPPRESSOR E-CADHERIN ; tumour suppression
    Abstract: Background: Smad4 is a tumour suppressor frequently inactivated in pancreatic and colorectal cancers. We have recently reported loss of Smad4 in every fourth carcinoma of the uterine cervix. Smad4 transmits signals from the TGF-beta superfamily of cytokines and functions as a versatile transcriptional co-modulator. The prevailing view suggests that the tumour suppressor function of Smad4 primarily resides in its capability to mediate TGF-beta growth inhibitory responses. However, accumulating evidence indicates, that the acquisition of TGF-beta resistance and loss of Smad4 may be independent events in the carcinogenic process. Through inducible reexpression of Smad4 in cervical cancer cells we wished to shed more light on this issue and to identify target genes implicated in Smad4 dependent tumor suppression. Methods: Smad4-deficient human C4-II cervical carcinoma cells were used to establish inducible Smad4 reexpression using the commercial Tet-on (TM) system (Clontech). The impact of Smad4 reexpression on cell growth was analysed in vitro and in vivo. Transcriptional responses were assessed through profiling on cDNA macroarrays (Clontech) and validated through Northern blotting. Results: Clones were obtained that express Smad4 at widely varying levels from approximately physiological to 50-fold overexpression. Smad4-mediated tumour suppression in vivo was apparent at physiological expression levels as well as in Smad4 overexpressing clones. Smad4 reexpression in a dose-dependent manner was associated with transcriptional induction of the extracellular matrix-associated genes, BigH3, fibronectin and PAI-I, in response to TGF-beta. Smad4-dependent regulation of these secreted Smad4 targets is not restricted to cervical carcinoma cells and was confirmed in pancreatic carcinoma cells reexpressing Smad4 after retroviral transduction and in a stable Smad4 knockdown model. On the other hand, the classical cell cycle-associated TGF-beta target genes, c-myc, p21 and p15, remained unaltered. Conclusion: Our results show that Smad4-mediated tumour suppression in cervical cancer cells is not due to restoration of TGF-beta growth inhibitory responses. Rather, tumour cell-ECM interactions may be more relevant for Smad4-mediated tumour suppression. C4-II cells with a high level inducible Smad4 expression may serve as a model to indicate further Smad4 targets responsive to diverse environmental stimuli operative in vivo
    Type of Publication: Journal article published
    PubMed ID: 17997817
    Signatur Availability
    BibTip Others were also interested in ...
  • 6
    Keywords: CELLS ; EXPRESSION ; GROWTH ; INVASION ; tumor ; TUMOR-CELLS ; carcinoma ; CELL ; Germany ; human ; COMMON ; GENE ; GENE-EXPRESSION ; GENES ; TUMORS ; TRANSDUCTION ; MECHANISM ; CARCINOGENESIS ; colon ; mechanisms ; BIOLOGY ; MEMBER ; MEMBERS ; MOLECULAR-BIOLOGY ; MOLECULE ; cytokines ; TARGET ; STAGE ; PROGRESSION ; MALIGNANCIES ; ENCODES ; MEMBRANE ; METASTASIS ; genetics ; COLORECTAL-CANCER ; COMPONENT ; inactivation ; EXTRACELLULAR-MATRIX ; ONCOGENE ; SUPERFAMILY ; CARCINOMAS ; beta-catenin ; GROWTH-FACTOR-BETA ; TARGETS ; TUMOR CELLS ; heredity ; REGULATOR ; FACTOR-BETA ; GAMMA-2 CHAIN ; CYTOKINE ; molecular biology ; molecular ; MATRIX ; CHAIN ; MALIGNANCY ; ONCOLOGY ; pancreas ; TUMOR-SUPPRESSOR ; basement membrane ; BASEMENT-MEMBRANE ; extracellular matrix ; secretion ; LEADS ; TRANSITION ; TGF-BETA ; pancreatic ; TUMOR-CELL ; SUPPRESSOR ; function ; COLON-CARCINOMA CELLS ; ENGLAND ; RECONSTITUTION ; LAMININ-5 ; CASCADE ; OCCURS ; Smad4 ; STABLE RNA INTERFERENCE ; DPC4 ; tumor suppressor Smad4
    Abstract: The tumor suppressor Smad4 is involved in carcinogenesis mainly of the pancreas and colon. Functional inactivation of Smad4 is a genetically late event that occurs upon transition from premalignant stages to invasive and metastatic growth. Smad4 encodes an intracellular messenger common to all signalling cascades induced by members of the transforming growth factor-beta (TGF-beta) superfamily of cytokines. Despite extensive knowledge about the mechanisms of TGF-beta/Smadsignal transduction, little is known about Smad4 targets involved in the transition to malignancy. The hallmark of invasive growth is a breakdown of the basement membrane ( BM), a specialized sheet of extracellular matrix produced through of epithelial and stromal cells. Laminin-5, a heterotrimeric epithelial-derived BM component, is commonly lost in carcinomas but not in premalignant tumors. Herein, we report that in human colon and pancreatic tumor cells, Smad4 functions as a positive transcriptional regulator of all three genes encoding laminin-5. Coordinate re-expression of the three laminin-5 chains induced by reconstitution of Smad4 leads to secretion and deposition of the heterotrimeric molecule in BM-like structures. These data de. ne the expression control of an essential BM component as a novel function for the tumor suppressor Smad4
    Type of Publication: Journal article published
    PubMed ID: 16953227
    Signatur Availability
    BibTip Others were also interested in ...
  • 7
    Keywords: CANCER ; Germany ; PATHWAY ; PATHWAYS ; NEW-YORK ; RISK ; GENE ; GENES ; PROTEIN ; PROTEINS ; GENETIC POLYMORPHISMS ; ASSOCIATION ; polymorphism ; POLYMORPHISMS ; SUSCEPTIBILITY ; BREAST ; breast cancer ; BREAST-CANCER ; NO ; mass spectrometry ; PCR ; MASS-SPECTROMETRY ; case-control studies ; ESTROGEN METABOLISM ; BRCA2 MUTATIONS ; CLUSTER ; POSTMENOPAUSAL WOMEN ; ONCOLOGY ; case-control study ; REGRESSION ; RE ; CATECHOL-O-METHYLTRANSFERASE ; HORMONE-REPLACEMENT THERAPY ; ESTROGEN ; analysis ; USA ; HAPLOTYPE RECONSTRUCTION ; CANDIDATE ; CANCER-RISK ; FRAGMENT ; COMT ; association analyses ; MULTIFACTOR-DIMENSIONALITY REDUCTION ; multivariate analyses
    Abstract: Polymorphisms within the estrogen metabolic pathway are prime candidates for a possible association with breast cancer risk. We investigated 11 genes encoding key proteins of this pathway for their potential contribution to breast cancer risk. Of these CYP17A1, CYP19A1, EPHX1, HSD17B1, SRD5A2, and PPARG2 participate in biosynthesis, CYP1A1, CYP1B1, COMT, GSTP1, and SOD2 in catabolism and detoxification. We performed a population-based case-control study with 688 incident breast cancer cases and 724 controls from Germany and genotyped 18 polymorphisms by matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), PCR based RFLP (restriction fragment length polymorphism), and TaqMan (R) allelic discrimination. Genotype frequencies were compared between cases and controls and odds ratios were calculated by conditional logistic regression. Further statistical analyses were based on cluster analysis, multifactor dimensionality reduction, logic regression, and global testing. Single factor analyses pointed to CYP1B1_1294_GG as a possible breast cancer risk modulator (OR = 2.57; 95% CI: 1.34-4.93) and two way stratification suggested associations between BMI 〉= 30 kg/m(2) and COMT_472_GG (P = 0.0076 and P = 0.0026), BMI 〈 20 kg/m(2) and HSD17B1_937_GG (P = 0.0082) as well as CYP17A1_-34_CC and HRT use 〉= 10 years (P = 0.0063). Following correction for multiple testing none of these associations remained significant. No significant association between breast cancer risk and genetic polymorphisms was observed in multifactor analyses. The tested polymorphisms of the estrogen metabolic pathway may not play a direct role in breast cancer risk. Therefore, future association studies should be extended to other polymorphisms and other regulatory pathways
    Type of Publication: Journal article published
    PubMed ID: 17588204
    Signatur Availability
    BibTip Others were also interested in ...
  • 8
    Keywords: CELLS ; GENES ; CHROMATIN ; DNA methylation ; BRAIN-TUMORS ; HIGH-GRADE GLIOMAS ; INTRINSIC PONTINE GLIOMAS ; COPY-NUMBER ABERRATIONS ; ONCOMETABOLITE 2-HYDROXYGLUTARATE ; HISTONE H3.3
    Abstract: Glioblastoma (GBM) is a brain tumor that carries a dismal prognosis and displays considerable heterogeneity. We have recently identified recurrent H3F3A mutations affecting two critical amino acids (K27 and G34) of histone H3.3 in one-third of pediatric GBM. Here, we show that each H3F3A mutation defines an epigenetic subgroup of GBM with a distinct global methylation pattern, and that they are mutually exclusive with IDH1 mutations, which characterize a third mutation-defined subgroup. Three further epigenetic subgroups were enriched for hallmark genetic events of adult GBM and/or established transcriptomic signatures. We also demonstrate that the two H3F3A mutations give rise to GBMs in separate anatomic compartments, with differential regulation of transcription factors OLIG1, OLIG2, and FOXG1, possibly reflecting different cellular origins.
    Type of Publication: Journal article published
    PubMed ID: 23079654
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...