Home About us Contact
|
Home About us Contact | ||
|
|
||
Expression Alterations (expression + alteration)
Selected AbstractsSignificance of Fas expression alteration during tumor progression of renal cell carcinomaINTERNATIONAL JOURNAL OF UROLOGY, Issue 3 2006TAKEHIRO SEJIMA Background:, In order to characterize the alteration of apoptotic regulatory molecule expression during tumor progression of renal cell carcinoma (RCC), we compared the expression between tumor and normal tissues, and evaluated the relationship of the expression in tumors with pathological and clinical characteristics. Methods:, Competitive reverse transcription,polymerase chain reaction (RT,PCR) and immunohistochemistry (IHC) allowed the determination of Fas and bcl-2 mRNA and protein expression in surgically resected tumor and normal tissue of 50 RCC. Results:, The mRNA expression of Fas and bcl-2 in RCC was significantly reduced compared to that in normal tissues. An IHC analysis was supportive of the RT,PCR results. In terms of relationships with pathological and clinical characteristics, the mRNA and protein expression of Fas in high-stage or high-grade tumors was significantly higher than that in low-stage or low-grade tumors. Moreover, a statistically poor prognosis was observed in tumor cases expressing a high amount of mRNA. In bcl-2 analysis, the mRNA and protein expression was significantly reduced in clear cell tumors compared to chromophobe cell tumors. Conclusion:, It is suggested that the reduced expression of Fas and bcl-2 in RCC compared with the expression in normal kidney is a prominent alteration of apoptotic regulatory molecules. The alteration of the up-regulated Fas expression might be characterized during the tumor progression stage. It is also suggested that the effect of alteration of bcl-2 expression might be minimal during the tumor progression stage because of the reduced expression in tumors of the clear cell type, which is the most dominant cell type in RCC. [source] The Aberrant Expressions of Nuclear Matrix Proteins During the Apoptosis of Human Osteosarcoma CellsTHE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 5 2010Zhen-Li Zhao Abstract The objective of this study was to investigate altered expressions of nuclear matrix proteins (NMPs) of human osteosarcoma (OS) MG-63 cells during curcumin-induced apoptosis of human OS MG-63 cells. MG-63 cells were cultured with curcumin (7.5 mg/L) for 72 hr. Morphological alterations of cells were captured using light microscopy and transmission electron microscopy, and cell cycle distribution was estimated by flow cytometry. NMPs were selectively extracted and subjected to two-dimensional gel electrophoresis (2-DE) analysis. Western blots were performed to determine changes in the expression levels of specific NMPs. The results demonstrated that typical characteristics of apoptosis were observed. Cellular chromatin agglutinated, cell nuclei condensed, and apoptotic bodies were formed after treatment with curcumin. The 2-DE results displayed 27 NMPs, 21 of which were identified to have change in expression levels significantly during apoptosis. The altered expressions of three of these NMPs (nucleophosmin, prohibitin, and vimentin) were further confirmed by immunoblotting. These findings indicated that the apoptosis of MG-63 cells was accompanied by the expression alteration of NMPs. Our results might help to reveal the relationship between NMPs and the regulation of gene expression in the process of apoptosis, as well as provide the basic concepts for future studies on the mechanisms of apoptosis and the therapy for bone diseases. Anat Rec, 2010. © 2010 Wiley-Liss, Inc. [source] The antiepileptic drug levetiracetam selectively modifies kindling-induced alterations in gene expression in the temporal lobe of ratsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2004Jessie Gu Abstract Gene expression profiling by microarrays is a powerful tool for identification of genes that may encode key proteins involved in molecular mechanisms underlying epileptogenesis. Using the Affymetrix oligonucleotide microarray, we have surveyed the expression levels of more than 26,000 genes and expressed sequence tags (ESTs) in the amygdala-kindling model of temporal lobe epilepsy. Furthermore, the effect of the antiepileptic drug levetiracetam (LEV) on kindling-induced alterations of gene expression was studied. Treatment of rats with LEV during kindling acquisition significantly suppressed kindling development. For gene expression profiling, six groups of rats were included in the present study: (i) and (ii) sham-operated rats treated with saline or LEV; (iii) and (iv) electrode-implanted but non-kindled rats treated with saline or LEV; (v) and (vi) kindled rats treated with saline or LEV. Treatment was terminated after 11 or 12 daily amygdala stimulations, when all vehicle-treated rats had reached kindling criterion, i.e. a stage 5 seizure. Twenty-four hours later, the ipsilateral temporal lobe was dissected for mRNA preparation. Six temporal lobe preparations from each group were analysed for differential gene expression. In control (non-kindled) rats, LEV treatment was devoid of any significant effect on gene expression. In saline-treated kindled rats, a large number of genes were observed to display mRNA expression alterations compared with non-kindled rats. LEV treatment induced marked effects on gene expression from kindled rats. Previously described epilepsy-related genes, such as neuropeptide Y (NPY), thyrotropin-releasing hormone (TRH) and glial fibrillary acidic protein (GFAP) were confirmed to be up-regulated by kindling and partially normalized by LEV treatment. Real-time quantitative polymerase chain reaction confirmed NPY, TRH and GFAP expression data from chip experiments. Furthermore, a number of novel genes were identified from the gene chip experiments. A subgroup of these genes demonstrated correlation between expression changes and kindled phenotype measurements. In summary, this study identified many genes with potentially important roles in epileptogenesis and highlighted several important issues in using the gene chip technology for the study of animal models of CNS disorders. [source] The gene for polycomb group protein enhancer of zeste homolog 2 (EZH2) is amplified in late-stage prostate cancerGENES, CHROMOSOMES AND CANCER, Issue 7 2006Outi R. Saramäki Overexpression of the polycomb group protein enhancer of zeste homologue 2 (EZH2) has been found in several malignancies, including prostate cancer, with an aggressive phenotype. Amplification of the gene has previously been demonstrated in several malignancies, but not in prostate cancer. Our goal was to evaluate the gene copy number and expression alterations of EZH2 in prostate cancer. The copy number of EZH2 in cell lines (LNCaP, DU145, PC-3, 22Rv1), xenografts (n = 10), and clinical tumors (n = 191) was studied with fluorescence in situ hybridization. All cell lines had a gain of EZH2. Eight of the ten xenografts showed an increased copy number of the gene, including one case of high-level amplification (,5 copies of the gene and EZH2/centromere ratio ,2). 34/125 (27%) of untreated prostate carcinomas showed increased copy number, but only one case of low-level amplification (,5 copies of the gene and EZH2/centromere ratio <2), whereas half (25/46) of the hormone-refractory carcinomas showed increased copy number, including seven cases of low-level amplification and three cases of high-level amplification (P < 0.0001). Expression of EZH2 was significantly (P = 0.0009) higher in hormone-refractory prostate cancer compared with that in benign prostatic hyperplasia or untreated cancer, according to quantitative real-time RT-PCR assay. Also, the expression of EZH2 protein was found to be higher in hormone-refractory tumors than in hormone-naïve tumors by immunohistochemistry. The EZH2 gene amplification was significantly (P < 0.05) associated with increased EZH2 protein expression. The data show that amplification of the EZH2 gene is rare in early prostate cancer, whereas a fraction of late-stage tumors contains the gene amplification leading to the overexpression of the gene, thus indicating the importance of EZH2 in the progression of prostate cancer. © 2006 Wiley-Liss, Inc. [source] Integrative molecular characterization of head and neck cancer cell model genomesHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 9 2010Ivy F. L. Tsui BSc Abstract Background. Cell lines are invaluable model systems for the investigation of cancer. Knowledge of the molecular alterations that exist within cell models is required to define the mechanisms governing cellular phenotypes. Methods. Five tongue squamous cell carcinomas cell lines and 1 submaxillary salivary gland epidermoid carcinoma cell line were analyzed for copy number and mRNA expression by tiling-path DNA microarrays and Agilent Whole Human Genome Oligoarrays, respectively. Results. Integrative analysis of genetic and expression alterations revealed the molecular landscape of each cell line. Molecular results for individual cell lines and across all samples have been summarized and made available for easy reference. Conclusion. Our integrative genomic analyses have defined the DNA and RNA alterations for each individual line. These data will be useful to anyone modeling oral cancer behavior, providing a molecular context that will be useful for deciphering cell phenotypes. © 2009 Wiley Periodicals, Inc. Head Neck, 2010 [source] Radiation-induced gene expression profile of human cells deficient in 8-hydroxy-2,-deoxyguanine glycosylaseINTERNATIONAL JOURNAL OF CANCER, Issue 3 2006M. Ahmad Chaudhry Abstract The human OGG1 gene encodes a DNA glycosylase that is involved in the base excision repair of 8-hydroxy-2,-deoxyguanine (8-OH-dG) from oxidatively damaged DNA. Cellular 8-OH-dG levels accumulate in the absence of this activity and could be deleterious for the cell. To assess the role of 8-oxoguanine glycosylase (OGG1) in the cellular defense mechanism in a specific DNA repair defect background, we set out to determine the expression pattern of base excision repair genes and other cellular genes not involved in the base excision pathway in OGG1-deficient human KG-1 cells after ionizing radiation exposure. KG-1 cells have lost OGG1 activity due to a homozygous mutation of Arg229Gln. Gene expression alterations were monitored at 4, 8, 12 and 24 hr in 2 Gy irradiated cells. Large-scale gene expression profiling was assessed with DNA microarray technology. Gene expression analysis identified a number of ionizing radiation-responsive genes, including several novel genes. There were 2 peaks of radiation-induced gene induction or repression: one at 8 hr and the other at 24 hr. Overall the number of downregulated genes was higher than the number of upregulated genes. The highest number of downregulated genes was at 8 hr postirradiation. Genes corresponding to cellular, physiologic, developmental and extracellular processes were identified. The highest number of radiation-induced genes belonged to the signal transduction category, followed by genes involved in transcription and response to stress. Microarray gene expression data were independently validated by relative quantitative RT-PCR. Surprisingly, none of the genes involved in the base excision repair of radiation-induced DNA damage showed altered expression. © 2005 Wiley-Liss, Inc. [source] Analysis of Aurora-A and hMPS1 mitotic kinases in mantle cell lymphomaINTERNATIONAL JOURNAL OF CANCER, Issue 2 2006Emma Camacho Abstract Aurora-A and hMPS1 are kinases involved in spindle checkpoint and centrosome duplication regulation and whose alterations have been associated with cell transformation and chromosome instability in different tumor models. In this study, we have examined the possible alterations of these genes in 58 mantle cell lymphomas (MCLs) and 4 MCL-related cell lines. Aurora-A was also examined in 46 diffuse large B-cell lymphomas (DLBCLs). Aurora-A and hMPS1 mRNA expression levels were related to tumor proliferative activity. Interestingly, a MCL case with the highest number or chromosomal imbalances also showed an extremely high value of Aurora-A mRNA expression. No Aurora-A gene amplifications were detected in any tumor or cell line, whereas hemizygous hMPS1 gene deletions were observed in 23% of MCLs and 3 of the 4 cell lines. However, no expression alterations or gene mutations were detected in these cases. The Aurora-A proposed cancer susceptibility polymorphic variant (P31I) was observed with a similar frequency in MCL, DLBCL, chronic lymphocytic leukemia and in the 431 healthy controls. However, the 3 MCLs and 4 DLBCLs with the homozygous variant of this polymorphism had particular clinical characteristics with an unusual early-age presentation and second epithelial malignancies in MCL and extranodal origin in DLBCL. These findings indicate that Aurora-A and hMPS1 aberrations are uncommon in aggressive lymphomas but Aurora-A overexpression may contribute to numerical chromosomal alterations in occasional MCL. Although the Aurora-A P31I polymorphic variant is not directly involved in a genetic predisposition to these lymphomas, it may modulate the clinical presentation of these tumors. © 2005 Wiley-Liss, Inc. [source] Transcriptional profiling of a mice plague model: insights into interaction between Yersinia pestis and its hostJOURNAL OF BASIC MICROBIOLOGY, Issue 1 2009Haihong Liu Abstract Despite the importance of pneumonic plague caused by Yersinia pestis, a few is known about the interaction between Y. pestis and its host at the molecular level during the pneumonic plague development. In this study, we employed an intranasally challenged plague model in mice for investigating the kinetics of the disease progression by transcriptional profiling of Y. pestis and mice using qRT-PCR and microarray, respectively. The increasing transcription of important virulence genes of Y. pestis and of mice genes involving in immune and inflammatory defensive responses, and responses to stimuli, presents an overview of interaction between Y. pestis and mice during development of pneumonic plague. The early and persisting up-regulation of caf 1, psa A and lcr V in vivo indicated their role in resisting the host innate immune responses. The up-regulation of fur, ybt A and hms H in vivo reflected the ability of Y. pestis for acquiring iron. The transcription regulators, including pho P, oxy R and omp R, were up-regulated during plague development, suggesting their roles in interaction between Y. pestis and mice. Many genes encoding cytokines, such as IL2, IL-1B, CXCL2, CXCL5, CCL20, CD14 and TNFRSF13B, were up-regulated during the infection, confirming the report that they are important mediators to activate host responses to invading pathogens. The up-regulation of some genes encoding important virulent factors of Y. pestis and expression alterations of some genes encoding cytokines in the host reflect the interaction between the pathogen and the host, which will help us better understand plague pathogenesis. (© 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] Behavioural and gene transcription alterations induced by spontaneous cannabinoid withdrawal in miceJOURNAL OF NEUROCHEMISTRY, Issue 1 2003José M. Oliva Abstract This study examined behavioural signs that occur during tolerance development to cannabinoid treatment and hormonal and gene expression alterations induced by spontaneous cannabinoid withdrawal in mice. Tolerance to CP-55,940 treatment developed for hypothermia, ambulatory and exploratory locomotor activity. Cessation of cannabinoid treatment resulted in a behavioural withdrawal syndrome characterized by a pronounced increase in ambulatory activity and rearings. Corticosterone plasma concentrations dramatically increased 24 and 72 h after cessation of cannabinoid treatment. Similarly, an increase (40%) in cannabinoid [35S]GTP,S binding autoradiography was detected on days 1 and 3 of abstinence. Spontaneous cannabinoid withdrawal produced time-related significant alterations in gene transcription: (i) decreased (20%) tyrosine hydroxylase (TH) mRNA levels in the ventral tegmental area and increased (50%) in substantia nigra; (ii) increased proenkephalin (PENK) gene expression more than 100% in caudate-putamen, nucleus accumbens, olfactory tubercle and piriform cortex; (iii) increased (20,40%) pro-opiomelanocortin (POMC) gene expression in the arcuate nucleus of the hypothalamus. These results suggest that spontaneous cannabinoid withdrawal occur after cessation of CP-55,940 treatment. This ,syndrome' includes behavioural, hormonal and gene transcription alterations that seems to be part of the regulation of neuronal plasticity induced by spontaneous cannabinoid withdrawal. [source] Effect of Rds abundance on cone outer segment morphogenesis, photoreceptor gene expression, and outer limiting membrane integrityTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 6 2007Rafal Farjo Abstract We examined the molecular, structural, and functional consequences on cone photoreceptors of the neural retinal leucine zipper knockout (Nrl,/,) mice when only one allele of retinal degeneration slow (Rds) is present (Rds+/,/Nrl,/,). Quantitative RT-PCR and immunoblot analysis were used to assess the expression levels of several phototransduction genes; electroretinography was used to assess quantitatively the retinal responsiveness to light; and immunohistochemistry and ultrastructural analysis were used to examine retinal protein distribution and morphology, respectively. In Rds/Nrl double-null mice, S-cones form dysmorphic outer segments that lack lamellae and fail to associate properly with the cone matrix sheath and the outer limiting membrane. In Rds+/,/Nrl,/, mice, cones form oversized and disorganized outer segment lamellae; although outer limiting membrane associations are maintained, normal interactions with cone matrix sheaths are not, and photoreceptor rosette formation is observed. These retinas produce significantly higher photopic a-wave and b-wave amplitudes than do those of Rds,/,/Nrl,/, mice, and the levels of several cone phototransduction genes are significantly increased coincidently with the presence of Rds and partial lamellae formation. Thus, as in rod photoreceptors, expression of only one Rds allele is unable to support normal outer segment morphogenesis in cones. However, cone lamellae assembly, albeit disorganized, concomitantly permits outer limiting membrane association, and this appears to be linked to photoreceptor rosette formation in the rodless (cone-only) Nrl,/, retina. In addition, photoreceptor gene expression alterations occur in parallel with changes in Rds levels. J. Comp. Neurol. 504:619,630, 2007. © 2007 Wiley-Liss, Inc. [source] Simultaneously detection of genomic and expression alterations in prostate cancer using cDNA microarray,THE PROSTATE, Issue 14 2008Mei Jiang Abstract BACKGROUND Prostate cancer is a common disease among men but the knowledge of the prostate carcinogenesis is still limited. METHODS cDNA microarray-based comparative genomic hybridization (CGH) and expression profiling were performed to screen the genomic and the expression changes in prostate cancer respectively. The two data were integrated to study the influence of genomic aberrations on gene expression and seek for the genes with their expression affected by the genomic aberrations. Real-time PCR was performed to evaluate the array data. RESULTS Array-based CGH detected gains at 2q, 3p/q, 5q, 6q, 8q, 9p, 10p/q, 11q, 12p, 14q, and 19p/q and losses at 1p, 2p, 4q, 6p/q, 7p, 11p/q, 12q, 17p/q, 19p/q, and Xp/q in more than 20% prostate tumors and narrowed these aberrations. For example, the gain of 8q was mapped to five minimal regions. Novel aberrations were also identified, such as loss at Xq21.33-q22.2. Expression profiling discovered the significant biological processes involved in the prostate carcinogenesis, such as exogenous antigen presentation via MHC class II and protein ubiquitination. Integration analysis revealed a weak positive correlation between genomic copy number and gene expression level. Fifty-three genes showed their expression directly affected by the genomic aberrations possibly, including more than one member of Ras superfamily and major histocompatibility complex (MHC). These genes are involved in multiple biological processes. CONCLUSIONS Integration of the CGH and expression data provided more information than separate analysis. Although the direct influence of genomic aberrations on gene expression seems weak, the influence can be extended by indirect regulation through a few directly affected genes. Because the influence can be persistent, the genes directly affected by the genomic aberrations may play key roles in the prostate carcinogenesis and are worth further analysis. Prostate 68: 1496,1509, 2008. © 2008 Wiley-Liss, Inc. [source] | |||||||||||||||||||||||||