scholarly journals Time-Qualified Patterns of Variation of PPARγ, DNMT1, and DNMT3B Expression in Pancreatic Cancer Cell Lines

PPAR Research ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Valerio Pazienza ◽  
Francesca Tavano ◽  
Massimo Francavilla ◽  
Andrea Fontana ◽  
Fabio Pellegrini ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Fate ◽  
Cell Lines ◽  
Expression Profiles ◽  
Dna Methyltransferases ◽  
Nutrient Sensing ◽  
Cell Phenotype ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Peroxisome Proliferator Activated Receptors

Carcinogenesis is related to the loss of homeostatic control of cellular processes regulated by transcriptional circuits and epigenetic mechanisms. Among these, the activities of peroxisome proliferator-activated receptors (PPARs) and DNA methyltransferases (DNMTs) are crucial and intertwined. PPARγis a key regulator of cell fate, linking nutrient sensing to transcription processes, and its expression oscillates with circadian rhythmicity. Aim of our study was to assess the periodicity of PPARγand DNMTs in pancreatic cancer (PC). We investigated the time-related patterns ofPPARG, DNMT1, andDNMT3Bexpression monitoring their mRNA levels by qRT-PCR at different time points over a 28-hour span in BxPC-3, CFPAC-1, PANC-1, and MIAPaCa-2 PC cells after synchronization with serum shock.PPARGandDNMT1expression in PANC-1 cells andPPARGexpression in MIAPaCa-2 cells were characterized by a 24 h period oscillation, and a borderline significant rhythm was observed for thePPARG, DNMT1, andDNMT3Bexpression profiles in the other cell lines. The time-qualified profiles of gene expression showed different shapes and phase relationships in the PC cell lines examined. In conclusion,PPARGandDNMTsexpression is characterized by different time-qualified patterns in cell lines derived from human PC, and this heterogeneity could influence cell phenotype and human disease behaviour.

scholarly journals The PPARα and PPARγ Epigenetic Landscape in Cancer and Immune and Metabolic Disorders

2021 ◽  
Vol 22 (19) ◽  
pp. 10573
Author(s):  
Jesús Porcuna ◽  
Jorge Mínguez-Martínez ◽  
Mercedes Ricote
Keyword(s):  
Metabolic Disorders ◽  
Target Genes ◽  
Dna Methyltransferases ◽  
Nutrient Sensing ◽  
Peroxisome Proliferator ◽  
Obesity And Diabetes ◽  
Histone Modifiers ◽  
Non Coding Rnas ◽  
Peroxisome Proliferator Activated Receptors ◽  
Epigenetic Modulation

Peroxisome proliferator-activated receptors (PPARs) are ligand-modulated nuclear receptors that play pivotal roles in nutrient sensing, metabolism, and lipid-related processes. Correct control of their target genes requires tight regulation of the expression of different PPAR isoforms in each tissue, and the dysregulation of PPAR-dependent transcriptional programs is linked to disorders, such as metabolic and immune diseases or cancer. Several PPAR regulators and PPAR-regulated factors are epigenetic effectors, including non-coding RNAs, epigenetic enzymes, histone modifiers, and DNA methyltransferases. In this review, we examine advances in PPARα and PPARγ-related epigenetic regulation in metabolic disorders, including obesity and diabetes, immune disorders, such as sclerosis and lupus, and a variety of cancers, providing new insights into the possible therapeutic exploitation of PPAR epigenetic modulation.

scholarly journals Correlations among PPAR, DNMT1, and DNMT3B Expression Levels and Pancreatic Cancer

PPAR Research ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Valerio Pazienza ◽  
Francesca Tavano ◽  
Giorgia Benegiamo ◽  
Manlio Vinciguerra ◽  
Francesca Paola Burbaci ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Perineural Invasion ◽  
Dna Methyltransferases ◽  
Pcr Analysis ◽  
Cell Phenotype ◽  
Peroxisome Proliferator ◽  
Expression Levels ◽  
Dnmt3b Expression

Emerging evidence indicates that peroxisome proliferator-activated receptorγ(PPARγ) and DNA methyltransferases (DNMTs) play a role in carcinogenesis. In this study we aimed to evaluate the expression of PPARγ, DNMT1, and DNMT3B and their correlation with clinical-pathological features in patients with pancreatic cancer (PC), and to define the effect of PPARγactivation on DNMTs expression in PC cell lines. qRT-PCR analysis showed that DNMT3B expression was downregulated in tumors compared to normal tissues (), whereas PPARγand DNMT1 levels did not show significant alterations in PC patients. Expression levels between PPARγand DNMT1 and between DNMT1 and DNMT3B were highly correlated ( and resp.). DNMT3B overexpression in tumor tissue was positively correlated with both lymph nodes spreading () and resection margin status (), and a borderline association with perineural invasion () was found. Furthermore, high levels of DNMT3B expression were significantly associated with a lower mortality in the whole population ( 95%–0.895, ) and in the subgroup of patients without perineural invasion (; 95%–0.758; ), while such association was not observed in patients with tumor invasion into perineural structures (). In conclusion,in vitroandin vivoPPARγand DNMTs appear interrelated in PC, and this interaction might influence cell phenotype and disease behavior.

scholarly journals Proton-irradiated breast cells: molecular points of view

2019 ◽  
Vol 60 (4) ◽  
pp. 451-465 ◽  
Author(s):  
Valentina Bravatà ◽  
Francesco P Cammarata ◽  
Luigi Minafra ◽  
Pietro Pisciotta ◽  
Concetta Scazzone ◽  
...  
Keyword(s):  
Cell Line ◽  
Cell Fate ◽  
Cell Lines ◽  
Molecular Mechanisms ◽  
Proton Irradiation ◽  
Expression Profiles ◽  
Treatment Plan ◽  
Mcf10a Cell ◽  
Specific Cell ◽  
Dose Dependent

Abstract Breast cancer (BC) is the most common cancer in women, highly heterogeneous at both the clinical and molecular level. Radiation therapy (RT) represents an efficient modality to treat localized tumor in BC care, although the choice of a unique treatment plan for all BC patients, including RT, may not be the best option. Technological advances in RT are evolving with the use of charged particle beams (i.e. protons) which, due to a more localized delivery of the radiation dose, reduce the dose administered to the heart compared with conventional RT. However, few data regarding proton-induced molecular changes are currently available. The aim of this study was to investigate and describe the production of immunological molecules and gene expression profiles induced by proton irradiation. We performed Luminex assay and cDNA microarray analyses to study the biological processes activated following irradiation with proton beams, both in the non-tumorigenic MCF10A cell line and in two tumorigenic BC cell lines, MCF7 and MDA-MB-231. The immunological signatures were dose dependent in MCF10A and MCF7 cell lines, whereas MDA-MB-231 cells show a strong pro-inflammatory profile regardless of the dose delivered. Clonogenic assay revealed different surviving fractions according to the breast cell lines analyzed. We found the involvement of genes related to cell response to proton irradiation and reported specific cell line- and dose-dependent gene signatures, able to drive cell fate after radiation exposure. Our data could represent a useful tool to better understand the molecular mechanisms elicited by proton irradiation and to predict treatment outcome

scholarly journals Expression Profiling of Nuclear Receptors in the NCI60 Cancer Cell Panel Reveals Receptor-Drug and Receptor-Gene Interactions

2010 ◽  
Vol 24 (6) ◽  
pp. 1287-1296 ◽  
Author(s):  
Susan Holbeck ◽  
Jianjun Chang ◽  
Anne M. Best ◽  
Angie L. Bookout ◽  
David J. Mangelsdorf ◽  
...  
Keyword(s):  
Drug Interactions ◽  
Cell Lines ◽  
Nuclear Receptors ◽  
Cancer Cell ◽  
Expression Profiling ◽  
Expression Profiles ◽  
Receptor Gene ◽  
Receptor Expression ◽  
Cancer Drug ◽  
Mrna Levels

Abstract We profiled the expression of the 48 human nuclear receptors (NRs) by quantitative RT-PCR in 51 human cancer cell lines of the NCI60 collection derived from nine different tissues. NR mRNA expression accurately classified melanoma, colon, and renal cancers, whereas lung, breast, prostate, central nervous system, and leukemia cell lines exhibited heterogeneous receptor expression. Importantly, receptor mRNA levels faithfully predicted the growth-inhibitory qualities of receptor ligands in nonendocrine tumors. Correlation analysis using NR expression profiles and drug response information across the cell line panel uncovered a number of new potential receptor-drug interactions, suggesting that in these cases, individual receptor levels may predict response to chemotherapeutic interventions. Similarly, by cross-comparing receptor levels within our expression dataset and relating these profiles to existing microarray gene expression data, we defined interactions among receptors and between receptors and other genes that can now be mechanistically queried. This work supports the strategy of using NR expression profiling to classify various types of cancer, define NR-drug interactions and receptor-gene networks, predict cancer-drug sensitivity, and identify druggable targets that may be pharmacologically manipulated for potential therapeutic intervention.

Prenatal androgen excess alters the uterine peroxisome proliferator-activated receptor (PPAR) system

2019 ◽  
Vol 31 (8) ◽  
pp. 1401
Author(s):  
Silvana R. Ferreira ◽  
Leandro M. Vélez ◽  
Maria F. Heber ◽  
Giselle A. Abruzzese ◽  
Alicia B. Motta
Keyword(s):  
Fetal Programming ◽  
Female Offspring ◽  
Control Group ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Androgen Excess ◽  
Peroxisome Proliferator Activated Receptor ◽  
Peroxisome Proliferator Activated Receptors ◽  
Pg E2 ◽  
Prenatal Androgen

It is known that androgen excess induces changes in fetal programming that affect several physiological pathways. Peroxisome proliferator-activated receptors (PPARs) α, δ and γ are key mediators of female reproductive functions, in particular in uterine tissues. Thus, we aimed to study the effect of prenatal hyperandrogenisation on the uterine PPAR system. Rats were treated with 2mg testosterone from Day 16 to 19 of pregnancy. Female offspring (PH group) were followed until 90 days of life, when they were killed. The PH group exhibited an anovulatory phenotype. We quantified uterine mRNA levels of PPARα (Ppara), PPARδ (Ppard), PPARγ (Pparg), their regulators peroxisome proliferator-activated receptor gamma coactivator 1-alpha (Ppargc1a) and nuclear receptor co-repressor 1 (Ncor1) and cyclo-oxygenase (COX)-2 (Ptgs2), and assessed the lipid peroxidation (LP) index and levels of glutathione (GSH) and prostaglandin (PG) E2. The PH group showed decreased levels of all uterine PPAR isoforms compared with the control group. In addition, PGE2 and Ptgs2 levels were increased in the PH group, which led to a uterine proinflammatory environment, as was LP, which led to a pro-oxidant status that GSH was not able to compensate for. These results suggest that prenatal exposure to androgen excess has a fetal programming effect that affects the gene expression of PPAR isoforms, and creates a misbalanced oxidant–antioxidant state and a proinflammatory status.

Lack of PRDM1α Expression in Hodgkin/Reed-Sternberg Cells Is Likely Mediated by a Translational or Post-Translational Mechanism.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4367-4367
Author(s):  
Wayne Tam ◽  
Leonard Tan ◽  
Mario Gomez ◽  
Shaoan Fan ◽  
Yifang Liu ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
B Cell ◽  
Cell Line ◽  
Cell Fate ◽  
Cell Lines ◽  
Western Blotting ◽  
Plasma Cell ◽  
Zinc Finger Protein ◽  
Cell Phenotype

Abstract Hodgkin/Reed Sternberg (H/RS) cells are the neoplastic cells in classical Hodgkin lymphoma (HL). They are thought to resemble post-germinal center (GC) B cells with expression of markers associated with late stage of B-cell differentiation, for example, interferon regulatory factor -4/multiple myeloma-1 (IRF4/MUM1) and syndecan 1 (CD138). The PR (PRDI-BF1-RIZ) domain zinc finger protein 1 (PRDM1), a transcription repressor with a master regulatory role in plasma cell differentiation, is normally co-expressed with IRF-4/MUM-1 in plasma cells and in a subset of activated GC cells committed to plasma cell fate. We studied expression of PRDM1α, the functional isoform of PRDM1, in 14 classical HL cases [including 3 positive for Epstein-Barr-virus (EBV)] and 4 HL cell lines by immunohistochemistry and Western blotting, respectively. H/RS cells in primary HL cases are negative for PRDM1α, implying a desynchrony in expression between IRF-4/MUM1 and PRDM1. While the myeloma cell line U266 expresses relatively abundant PRDM1α, it was undetectable by Western Blotting in all HL cell lines tested, except for the EBV-positive HL cell line L591 which, unlike in vivo H/RS cells, has a Type III EBV latency pattern. PRDM1α expression in L591 but not in vivo H/RS cells suggests that PRDM1 expression may be modulated by latency type-specific EBV-encoded gene products or the B-cell phenotype exhibited by the cell line. The lack of PRDM1α protein in H/RS cells is not due to impaired gene transcription, since real-time quantitative PCR revealed similarly abundant PRDM1α transcripts in the HL cell lines as U266. In the absence of mutation in the PRDM1 coding region, these results suggest that failure to accumulate PRDM1α protein in H/RS cells is likely due to abnormal translation repression or protein turnover. Loss of functional PRDM1 as a result of translational or post-translational deregulation may represent a novel molecular lesion in HL.

New Pathogenetic Insights Into Classical Hodgkin Lymphoma Revealed by Gene Expression Profiling of Microdissected Hodgkin/Reed-Sternberg Cells.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 266-266 ◽  
Author(s):  
Enrico Tiacci ◽  
Verena Brune ◽  
Susan Eckerle ◽  
Wolfram Klapper ◽  
Ines Pfeil ◽  
...  
Keyword(s):  
Gene Expression ◽  
B Cells ◽  
B Cell ◽  
Gene Expression Profiling ◽  
Hodgkin Lymphoma ◽  
Cell Lines ◽  
Expression Profiling ◽  
Expression Profiles ◽  
B Cell Lymphoma ◽  
Cell Phenotype

Abstract Abstract 266 Background. Previous gene expression profiling studies on cHL have been performed on whole tissue sections (mainly reflecting the prominent reactive background in which the few HRS cells are embedded), or on cHL cell lines. However, cultured HRS cells do not likely reflect primary HRS cells in all aspects, being derived from end-stage patients and from sites (e.g. pleural effusions or bone marrow) which are not typically involved by cHL and where HRS cells lost their dependence on the inflammatory microenvironment of the lymph node. Methods. ∼1000–2000 neoplastic cells were laser-microdissected from hematoxylin/eosin-stained frozen sections of lymph nodes taken at disease onset from patients with cHL (n=16) or with various B-cell lymphomas (n=35), including primary mediastinal B-cell lymphoma (PMBL) and nodular lymphocyte-predominant Hodgkin lymphoma (nLPHL). After two rounds of in vitro linear amplification, mRNA was hybridized to Affymetrix HG-U133 Plus 2.0 chips. Expression profiles were likewise generated from sorted cHL cell lines and several normal mature B-cell populations. Results. Primary and cultured HRS cells, although sharing hallmark cHL signatures such as high NF-kB transcriptional activity and lost B-cell identity, showed considerable transcriptional divergence in chemokine/chemokine receptor activity, extracellular matrix remodeling and cell adhesion (all enriched in primary HRS cells), as well as in proliferation (enriched in cultured HRS cells). Unsupervised and supervised analyses indicated that microdissected HRS cells of cHL represent a transcriptionally unique lymphoma entity, overall closer to nLPHL than to PMBL but with differential behavior of the cHL histological subtypes, being HRS cells of the lymphocyte-rich and mixed-cellularity subtypes close to nLPHL cells while HRS cells of NS and LD exhibited greater similarity to PMBL cells. HRS cells downregulated a large number of genes involved in cell cycle checkpoints and in the maintenance of genomic integrity and chromosomal stability, while upregulating gene and gene signatures involved in various oncogenic signaling pathways and in cell phenotype reprogramming. Comparisons with normal B cells highlighted the lack of consistent transcriptional similarity of HRS cells to bulk germinal center (GC) B cells or plasma cells and, interestingly, a more pronounced resemblance to CD30+ GC B cells and CD30+ extrafollicular B cells, two previously uncharacterized subsets that are transcriptionally distinct from the other mature B-cell types. Conclusions. Gene expression profiling of primary HRS cells provided several new insights into the biology and pathogenesis of cHL, its relatedness to other lymphomas and normal B cells, and its enigmatic phenotype. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Modulation of peroxisome proliferator-activated receptor δ and γ transcripts in swine endometrial tissue during early gestation

Reproduction ◽  
2006 ◽  
Vol 131 (5) ◽  
pp. 929-942 ◽  
Author(s):  
Etienne Lord ◽  
Bruce D Murphy ◽  
Joëlle A Desmarais ◽  
Sandra Ledoux ◽  
Danièle Beaudry ◽  
...  
Keyword(s):  
Embryo Implantation ◽  
Endometrial Tissue ◽  
Pcr Analysis ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Tissue Sampling ◽  
Peroxisome Proliferator Activated Receptor ◽  
Attachment Sites ◽  
Peroxisome Proliferator Activated Receptors ◽  
Implantation Period

Recent evidence points to a role for peroxisome proliferator-activated receptors (PPARs) δ and γ in embryo implantation and survival. In this study, we report the porcine PPARδ complete coding sequence and mRNA abundance of PPARδ, PPARγ1 and γ2, angiopoietin-like protein 4 (ANGPTL4) and adipocyte determination and differentiation-dependent factor 1 (ADD1) genes in the pregnant sow endometrium. Real-time PCR analysis was used to study the effect of parity (Yorkshire-Landrace multiparous (YL) and nulliparous (YLn)), site of endometrial tissue sampling (between and at embryo attachment sites) in crossbred Duroc×Yorkshire-Landrace (DYL) sows and stages of pregnancy (non-pregnant, day 15 and day 25 after mating) in Meishan-Landrace (ML) on mRNA levels. Parity effects were observed for PPARδ, ANGPTL4, and ADD1, with higher mRNA levels in YL than YLn sows. In DYL sows, lower mRNA levels were present at attachment sites compared to between attachment sites for PPARδ, PPARγ1, and ANGPTL4. Finally, day 15 pregnant ML sows had lower PPARδ mRNA levels compared to day 15 cycling ML sows. A significant increase of PPARγ1 mRNA levels was found on day 25 pregnant ML and DYL sows relative to day 15 ML or DYL pregnant sows. PPARδ and γ immunostaining was detected in endometrial tissue of day 15 cycling sows, day 15 and 25 pregnant sows and epithelial cells of day 25 embryos. Collectively, our results suggest a role for PPARδ, PPARγ1, and ANGPTL4, but not PPARγ2, during the peri-implantation period in pregnant sows.

scholarly journals Discovery and Validation of Circulating EVL mRNA as a Prognostic Biomarker in Pancreatic Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Yan Du ◽  
Kai Yao ◽  
Qingbo Feng ◽  
Feiyu Mao ◽  
Zechang Xin ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Mrna Expression ◽  
Cox Regression ◽  
Expression Profiles ◽  
Differentially Expressed ◽  
Cancer Type ◽  
Mrna Levels ◽  
Plasma Samples ◽  
Patient Prognosis

Background. Circulating plasma mRNAs can be analyzed to identify putative cancer biomarkers. This study was conducted in an effort to detect plasma mRNA biomarkers capable of predicting pancreatic cancer (PACA) patient prognosis. Material and Methods. First, prognostic mRNAs that were differentially expressed in PACA in The Cancer Genome Atlas (TCGA) were established, after which microarray expression profiles from PACA patient plasma samples were utilized to specifically identify potential prognostic plasma mRNA biomarkers associated with this cancer type. In total, plasma samples were then collected from 79 PACA patients and 19 healthy controls to confirm differential mRNA expression via qPCR, while Kaplan–Meier analyses were used to examine the link between mRNA expression and patient overall survival. Results. In total, three prognostic differentially expressed genes were identified in PACA patient plasma samples, including SMAP2, PTPN6, and EVL (Ena/VASP-like). Plasma EVL levels were confirmed via qPCR to be correlated with tumor pathology p < 0.01 , while the overall survival of patients with low plasma EVL levels was poor p < 0.01 . Multivariate Cox regression analyses further confirmed that plasma EVL levels were independent predictors of PACA patient prognosis. Conclusion. We found that PACA is associated with the downregulation of plasma EVL mRNA levels, indicating that this mRNA may be a viable biomarker associated with patient prognosis.

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