scholarly journals Expression Signature of the Mouse Prostate

2005 ◽  
Vol 280 (43) ◽  
pp. 36442-36451 ◽  
Author(s):  
Isabelle M. Berquin ◽  
Younong Min ◽  
Ruping Wu ◽  
Hong Wu ◽  
Yong Q. Chen
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Critical Role ◽  
Actin Binding ◽  
Migration And Invasion ◽  
Gene Expression Patterns ◽  
Normal Prostate ◽  
Mouse Prostate ◽  
Genetically Engineered Mice

Genetically engineered mice are being used increasingly for delineating the molecular mechanisms of prostate cancer development. Epithelium-stroma interactions play a critical role in prostate development and tumorigenesis. To better understand gene expression patterns in the normal sexually mature mouse prostate, epithelium and stroma were laser-capture microdissected from ventral, dorsolateral, and anterior prostate lobes. Genome-wide expression was measured by DNA microarrays. Our analysis indicated that the gene expression pattern in the mouse dorsolateral lobe was closest to that of the human prostate peripheral zone, supporting the hypothesis that these prostate compartments are functionally equivalent. Stroma from a given lobe had closer gene expression patterns with stroma from other lobes than epithelium from the same lobe. Stroma appeared to have higher expression complexity than epithelium. Specifically, stromal cells had higher expression levels of genes implicated in cell adhesion, muscle development, and contraction, in structural constituents of cytoskeleton and actin binding, and in components such as sarcomere and extracellular matrix collagen. Among the genes that were enriched in the epithelium were secretory proteins, including seminal vesicle protein secretion 2 and 5. Surprisingly, prostate stroma expressed many osteogenic molecules, as confirmed by immunohistochemistry. A “bone-like” environment in the prostate may predispose prostate cells for survival in the bone. Chemokine Cxcl12 but not its receptor, Cxcr4, was expressed in normal prostate. In prostate tumors, interestingly, Cxcl12 was up-regulated in epithelial cells with a concomitant expression of Cxcr4. Expression of both the receptor and ligand may provide an autocrine mechanism for tumor cell migration and invasion.

scholarly journals Unraveling the molecular heterogeneity in type 2 diabetes: A potential subtype discovery study followed by metabolic modeling

2020 ◽  
Author(s):  
Maryam Khoshnejat ◽  
Kaveh Kavousi ◽  
Ali Mohammad Banaei-Moghaddam ◽  
Ali Akbar Moosavi-Movahedi
Keyword(s):  
Gene Expression ◽  
Type 2 Diabetes ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Critical Role ◽  
Gene Expression Pattern ◽  
Gene Expression Patterns ◽  
Diabetic Patients ◽  
Molecular Heterogeneity

Abstract BackgroundType 2 diabetes mellitus (T2DM) is a complex multifactorial disease with a high prevalence in the world. Insulin resistance and impaired insulin secretion are the two major abnormalities in the pathogenesis of T2DM. Skeletal muscle is responsible for over 75% of the glucose uptake, thus plays a critical role in T2DM. Here, we attempted to provide a better understanding of abnormalities in this tissue. MethodsThe muscle gene expression patterns in healthy and newly diagnosed T2DM individuals were explored using supervised and unsupervised classification approach. Moreover, the potential of sub-typing T2DM patients based on the gene expression patterns was evaluated.ResultsA machine-learning technique was applied to identify a gene expression pattern that could discriminate between normoglycemic and diabetic groups. A gene set comprises of 26 genes was found that was able to discriminate healthy from diabetic individuals with 94% accuracy. In addition, three distinct clusters of diabetic patients with different dysregulated genes and metabolic pathways were identified. Conclusions This study implies that it seems the disease has triggered through different cellular/molecular mechanisms, and it has the potential to be categorized in different sub-types. Possibly, subtyping of T2DM patients in combination with their real clinical profiles will provide a better understanding of abnormalities in each group. Thus, this approach will help to recommend the appropriate treatment for each subtype in the future.

scholarly journals Unraveling the molecular heterogeneity in type 2 diabetes: A potential subtype discovery followed by metabolic modeling

2020 ◽  
Author(s):  
Maryam Khoshnejat ◽  
Kaveh Kavousi ◽  
Ali Mohammad Banaei-Moghaddam ◽  
Ali Akbar Moosavi-Movahedi
Keyword(s):  
Gene Expression ◽  
Type 2 Diabetes ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Critical Role ◽  
Unsupervised Classification ◽  
Gene Expression Patterns ◽  
Diabetic Patients ◽  
Molecular Heterogeneity

Abstract BackgroundType 2 diabetes mellitus (T2DM) is a complex multifactorial disease with a high prevalence worldwide. Insulin resistance and impaired insulin secretion are the two major abnormalities in the pathogenesis of T2DM. Skeletal muscle is responsible for over 75% of the glucose uptake and plays a critical role in T2DM. Here, we sought to provide a better understanding of the abnormalities in this tissue. MethodsThe muscle gene expression patterns were explored in healthy and newly diagnosed T2DM individuals using supervised and unsupervised classification approaches. Moreover, the potential of subtyping T2DM patients was evaluated based on the gene expression patterns.ResultsA machine-learning technique was applied to identify a set of genes whose expression patterns could discriminate diabetic subjects from healthy ones. A gene set comprising of 26 genes was found that was able to distinguish healthy from diabetic individuals with 94% accuracy. In addition, three distinct clusters of diabetic patients with different dysregulated genes and metabolic pathways were identified. Conclusions This study indicates that T2DM is triggered by different cellular/molecular mechanisms, and it can be categorized into different subtypes. Subtyping of T2DM patients in combination with their real clinical profiles will provide a better understanding of the abnormalities in each group and more effective therapeutic approaches in the future.

scholarly journals Gene Expression Patterns Underlying the Reinstatement of Plasticity in the Adult Visual System

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Ettore Tiraboschi ◽  
Ramon Guirado ◽  
Dario Greco ◽  
Petri Auvinen ◽  
Jose Fernando Maya-Vetencourt ◽  
...  
Keyword(s):  
Gene Expression ◽  
Visual Cortex ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Monocular Deprivation ◽  
Adult Brain ◽  
Gene Expression Patterns ◽  
Postnatal Life ◽  
Critical Periods

The nervous system is highly sensitive to experience during early postnatal life, but this phase of heightened plasticity decreases with age. Recent studies have demonstrated that developmental-like plasticity can be reactivated in the visual cortex of adult animals through environmental or pharmacological manipulations. These findings provide a unique opportunity to study the cellular and molecular mechanisms of adult plasticity. Here we used the monocular deprivation paradigm to investigate large-scale gene expression patterns underlying the reinstatement of plasticity produced by fluoxetine in the adult rat visual cortex. We found changes, confirmed with RT-PCRs, in gene expression in different biological themes, such as chromatin structure remodelling, transcription factors, molecules involved in synaptic plasticity, extracellular matrix, and excitatory and inhibitory neurotransmission. Our findings reveal a key role for several molecules such as the metalloproteases Mmp2 and Mmp9 or the glycoprotein Reelin and open up new insights into the mechanisms underlying the reopening of the critical periods in the adult brain.

Physical activity and prostate gene expression in men with low-risk prostate cancer.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 189-189 ◽  
Author(s):  
Mark Jesus Mendoza Magbanua ◽  
Erin L Richman ◽  
Eduardo V Sosa ◽  
Lee Jones ◽  
Jeffrey Simko ◽  
...  
Keyword(s):  
Gene Expression ◽  
Physical Activity ◽  
Prostate Cancer ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Low Risk ◽  
Normal Prostate ◽  
Pathway Gene ◽  
Risk Prostate Cancer ◽  
Low Risk Prostate Cancer

189 Background: Physical activity (PA), in particular longer duration or higher intensity, may reduce the risk of PCa progression and PCa-specific mortality in men diagnosed with clinically localized PCa. However, the molecular mechanism(s) by which PA exerts its protective effect in the prostate remains unknown. We examined the correlation of PA and gene expression patterns in men with low risk prostate cancer who elected to undergo active surveillance. Methods: Morphologically normal prostate tissue was obtained from men who subsequently participated in a clinical trial focused on nutritional supplements (previously published microarray dataset #GSE27140). Of the original sample (n=84), 70 completed a brief PA questionnaire and were dichotomized based usual PA [e.g. any vigorous PA (yes/no), 3+ h/wk vigorous PA (yes/no)]. Differential expression and pathway (gene set) analyses between groups were performed using Significance Analysis of Microarrays. Genes and gene sets with a false discovery rate ≤0.10 and 0.20 were considered significant, respectively. Results: Gene expression analysis detected 184 significant genes that were differentially expressed between men who performed vigorous PA for 3+ h/wk (n=23) and those who did not (n= 47). Up-regulated genes included the known tumor suppressors, BRCA1 and BRCA2. Furthermore, pathway analysis revealed that cell cycle and DNA repair pathways were positively modulated in men who participated in 3+h/wk vigorous PA vs. not. Consistent with the data on vigorous PA and clinical outcomes in men with PCa, the duration of vigorous PA was important; there were no significant genes detected when comparing men who participated in any vigorous PA to men who did none. Conclusions: Prostate gene expression and pathway analyses revealed candidate genes and in vivo pathways that may be modulated by participating in 3+ h/wk of vigorous PA. These data provide mechanistic insight into how 3+ h/wk of vigorous PA may offer PCa-specific benefits. Furthermore, understanding the molecular mechanisms by which such PA affects normal prostate gene expression may aid the development of strategies to prevent or delay PCa progression.

scholarly journals Losing maternal care: Neotenic gene expression in the preoptic area of avian brood parasites

2018 ◽  
Author(s):  
Kathleen S. Lynch ◽  
Lauren A. O’Connell ◽  
Matthew I. M. Louder ◽  
Anthony Pellicano ◽  
Annmarie Gaglio ◽  
...  
Keyword(s):  
Gene Expression ◽  
Parental Care ◽  
Maternal Behavior ◽  
Brood Parasitism ◽  
Large Scale ◽  
Preoptic Area ◽  
Expression Patterns ◽  
Critical Role ◽  
Gene Expression Patterns ◽  
Brood Parasites

AbstractParental care for is critical for offspring survival in many species. However, parental behaviors have been lost in roughly 1% of avian species known as the obligate brood parasites. To shed light on molecular and neurobiological mechanisms mediating brood parasitic behavior, brain gene expression patterns between two brood parasitic species and one closely related non-parasitic Icterid (blackbird) species were compared. Our analyses focused on gene expression changes specifically in the preoptic area (POA), a brain region known to play a critical role in maternal behavior across vertebrates. Using comparative transcriptomic approaches, we identified gene expression patterns associated with brood parasitism and evaluated two alternative explanations for the evolution of brood parasitism: reduced expression of parental-related genes in the POA versus retention of juvenile (neotenic) gene expression. While we did not find evidence for large scale gene downregulation, expression patterns did reflect substantial evidence for neotenic POA gene expression in parasitic birds. Differentially expressed genes with previously established roles in parental care were identified. Targeted examination of these selected candidate genes in additional hypothalamic regions revealed species differences in gene expression patterns is not POA-specific. Together, these results provide new insights into neurogenomics underlying maternal behavior loss in avian brood parasites.

scholarly journals Time course Analysis of Gene expression patterns in ZebrafIsh Eye during Optic Nerve Regeneration

2010 ◽  
Vol 4 ◽  
pp. JEN.S5006 ◽  
Author(s):  
Amy T. Mccurley ◽  
Gloria V. Callard
Keyword(s):  
Gene Expression ◽  
Optic Nerve ◽  
Nerve Regeneration ◽  
Time Course ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Gene Expression Patterns ◽  
Neural Cells ◽  
Nerve Crush ◽  
Optic Nerve Regeneration

It is well-established that neurons in the adult mammalian central nervous system (CNS) are terminally differentiated and, if injured, will be unable to regenerate their connections. In contrast to mammals, zebrafish and other teleosts display a robust neuroregenerative response. Following optic nerve crush (ONX), retinal ganglion cells (RGC) regrow their axons to synapse with topographically correct targets in the optic tectum, such that vision is restored in ~21 days. What accounts for these differences between teleostean and mammalian responses to neural injury is not fully understood. A time course analysis of global gene expression patterns in the zebrafish eye after ONX can help to elucidate cellular and molecular mechanisms that contribute to a successful neuroregeneration. To define different phases of regeneration after ONX, alpha tubulin 1 ( tuba1) and growth-associated protein 43 ( gap43), markers previously shown to correspond to morphophological events, were measured by real time quantitative PCR (qPCR). Microarray analysis was then performed at defined intervals (6 hours, 1, 4, 12, and 21 days) post-ONX and compared to SHAM. Results show that optic nerve damage induces multiple, phase-related transcriptional programs, with the maximum number of genes changed and highest fold-change occurring at 4 days. Several functional groups affected by optic nerve regeneration, including cell adhesion, apoptosis, cell cycle, energy metabolism, ion channel activity, and calcium signaling, were identified. Utilizing the whole eye allowed us to identify signaling contributions from the vitreous, immune and glial cells as well as the neural cells of the retina. Comparisons between our dataset and transcriptional profiles from other models of regeneration in zebrafish retina, heart and fin revealed a subset of commonly regulated transcripts, indicating shared mechanisms in different regenerating tissues. Knowledge of gene expression patterns in all components of the eye in a model of successful regeneration provides an entry point for functional analyses, and will help in devising hypotheses for testing normal and toxic regulatory factors.

scholarly journals Analysis by cDNA microarrays of gene expression patterns of human adrenocortical tumors

2006 ◽  
Vol 154 (4) ◽  
pp. 587-598 ◽  
Author(s):  
E P Slater ◽  
S M Diehl ◽  
P Langer ◽  
B Samans ◽  
A Ramaswamy ◽  
...  
Keyword(s):  
Gene Expression ◽  
Comparative Analysis ◽  
Normal Tissue ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Malignant Neoplasm ◽  
Cdna Microarrays ◽  
Gene Expression Patterns ◽  
Chromogranin B ◽  
Adrenocortical Tumors

Objectives: Adrenocortical carcinoma (ACC) is a rare malignant neoplasm with extremely poor prognosis. The molecular mechanisms of adrenocortical tumorigenesis are still not well understood. The comparative analysis by cDNA microarrays of gene-expression patterns of benign and malignant adrenocortical tumors allows us to identify new tumor-suppressor genes and proto-oncogenes underlying adrenocortical tumorigenesis. Design and methods: Total RNA from fresh-frozen tissue of 10 ACC and 10 benign adrenocortical adenomas was isolated after histologic confirmation of neoplastic cellularity of at least 85%. The reference consisted of pooled RNA of 10 normal adrenal cortex samples. Amplified RNA of tumor and reference was used to synthesize Cy3- and Cy5-fluorescently labeled cDNA in a flip-color technique. D-chips containing 11 540 DNA spots were hybridized and scanned and the images were analyzed by ImaGene 3.0 software. Results: The comparative analysis of gene expression revealed many genes with more than fourfold expression difference between ACC and normal tissue (42 genes), cortical adenoma and normal tissue (11 genes), and ACC and cortical adenoma (21 genes) respectively. As confirmed by real-time PCR, the IGF2 gene was significantly upregulated in ACCs versus cortical adenomas and normal cortical tissue. Genes that were downregulated in adrenocortical tumors included chromogranin B and early growth response factor 1. Conclusions: Comprehensive expression profiling of adrenocortical tumors by the cDNA microarray technique is a very powerful tool to elucidate the molecular steps associated with the tumorigenesis of these ill-defined neoplasms. To evaluate the role of identified genes, further detailed analyses, including correlation with clinical data, are required.

scholarly journals Differential responses in placenta and fetal thymus at 12 days post infection elucidate mechanisms of viral level and fetal compromise following PRRSV2 infection

BMC Genomics ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Angelica Van Goor ◽  
Alex Pasternak ◽  
Kristen Walker ◽  
Linjun Hong ◽  
Carolina Malgarin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Fetal Outcome ◽  
Respiratory Syndrome Virus ◽  
Gene Expression Patterns ◽  
Fetal Thymus ◽  
Fetal Infection ◽  
Significant Step ◽  
Inducible Genes

Abstract Background A pregnant gilt infected with porcine reproductive and respiratory syndrome virus (PRRSV) can transmit the virus to her fetuses across the maternal-fetal-interface resulting in varying disease outcomes. However, the mechanisms leading to variation in fetal outcome in response to PRRSV infection are not fully understood. Our objective was to assess targeted immune-related gene expression patterns and pathways in the placenta and fetal thymus to elucidate the molecular mechanisms involved in the resistance/tolerance and susceptibility of fetuses to PRRSV2 infection. Fetuses were grouped by preservation status and PRRS viral load (VL): mock infected control (CTRL), no virus detected (UNINF), virus detected in the placenta only with viable (PLCO-VIA) or meconium-stained fetus (PLCO-MEC), low VL with viable (LVL-VIA) or meconium-stained fetus (LVL-MEC), and high VL with viable (HVL-VIA) or meconium-stained fetus (HVL-MEC). Results The host immune response was initiated only in fetuses with detectable levels of PRRSV. No differentially expressed genes (DEG) in either the placenta or thymus were identified in UNINF, PLCO-VIA, and PLCO-MEC when compared to CTRL fetuses. Upon fetal infection, a set of core responsive IFN-inducible genes (CXCL10, IFIH1, IFIT1, IFIT3, ISG15, and MX1) were strongly upregulated in both tissues. Gene expression in the thymus is a better differentiator of fetal VL; the strong downregulation of several innate and adaptive immune pathways (e.g., B Cell Development) are indicative of HVL. Gene expression in the placenta may be a better differentiator of fetal demise than the thymus, based-on principle component analysis clustering, gene expression patterns, and dysregulation of the Apoptosis and Ubiquitination pathways. Conclusion Our data supports the concept that fetal outcome in response to PRRSV2 infection is determined by fetal, and more significantly placental response, which is initiated only after fetal infection. This conceptual model represents a significant step forward in understanding the mechanisms underpinning fetal susceptibility to the virus.

scholarly journals Loss of HuR Is Linked to Reduced Expression of Proliferative Genes during Replicative Senescence

2001 ◽  
Vol 21 (17) ◽  
pp. 5889-5898 ◽  
Author(s):  
Wengong Wang ◽  
Xiaoling Yang ◽  
Vincent J. Cristofalo ◽  
Nikki J. Holbrook ◽  
Myriam Gorospe
Keyword(s):  
Gene Expression ◽  
Rna Binding ◽  
Replicative Senescence ◽  
Binding Protein ◽  
Expression Patterns ◽  
Critical Role ◽  
Rna Binding Protein ◽  
Cellular Aging ◽  
Gene Expression Patterns ◽  
Senescent Phenotype

ABSTRACT Cellular aging is accompanied by alterations in gene expression patterns. Here, using two models of replicative senescence, we describe the influence of the RNA-binding protein HuR in regulating the expression of several genes whose expression decreases during senescence. We demonstrate that HuR levels, HuR binding to target mRNAs encoding proliferative genes, and the half-lives of such mRNAs are lower in senescent cells. Importantly, overexpression of HuR in senescent cells restored a “younger” phenotype, while a reduction in HuR expression accentuated the senescent phenotype. Our studies highlight a critical role for HuR during the process of replicative senescence.

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