DOCSLIB.ORG

Hereditary/Familial Versus Sporadic Prostate Cancer: Few Indisputable Genetic Differences and Many Similar Clinicopathological Features

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Hereditary/Familial Versus Sporadic Prostate Cancer: Few Indisputable Genetic Differences and Many Similar Clinicopathological Features European Review for Medical and Pharmacological Sciences 2010; 14: 31-41 Hereditary/familial versus sporadic prostate cancer: few indisputable genetic differences and many similar clinicopathological features C. ALBERTI Surgical Semeiotics, University of Parma, Parma (Italy) Abstract. – Genetic factors and their inter- VDR gene, that is a component of ligand actions with environmental conditions and inter- (steroid)-dependent nuclear transcription factor nal microenvironment influence the prostate superfamily, shows various polymorphisms cancer (PC) development, so that gene expres- which appear to be associated with PC risk. Ex- sion couldn’t strictly occur on the basis of re- cept an earlier age of onset, no anatomo-clinical ductionist determinisms of DNA causality but and tumor progression peculiarities between should also conform to multifactorial and sto- hereditary and sporadic PC have been generally chastic events, moreover, considering the pre- identified. Indeed, tumor progression and metas- RNA alternative splicing-mediated multi-protein tasis, both in hereditary and sporadic PC, are assemblying mechanisms. Nevertheless, after mainly influenced by a variety of biochemical age and ethnic background, the strongest epi- and immune-mediated tumor microenvironmen- demiological risk factor for PC is a positive fami- tal conditions rather than by the hereditary ge- ly history. However, apart from RNaseL-, ElaC2-, netic factors, thus gene expression associated MSR1-genes, there are not other identified high- with invasive ability representing a newly ac- risk genetic variants which might be considered quired genetic variant rather than a selection of responsible for hereditary PC, moreover sug- pre-existent gene abnormalities in PC cells. It’s gesting that familial PC is a genetically hetero- questionable whether genetic testing of unaf- geneous disease, many gene loci rather than a fected men of hereditary PC families might be specific major susceptibility gene predisposing actually useful. Nevertheless a suitable coun- to it. Gene-environment interactions play a cru- selling must be proposed. Family history and/or cial role in cancer development especially when gene profiling-guided preventive strategies for low penetrance genes, such as in case of genet- men at high risk of familial PC, range from di- ic polymorphisms, are the major players. Several etary to drug measures. Cancer chemopreven- epidemiological studies show, in some families, tive approaches may include 5-α-reductase in- a possible, either syncronous or metachronous, hibitors, histone deacetylase inhibitors, antioxi- association of other tumors (breast, brain, gas- dans, non-steroidal anti-inflammatory drugs, trointestinal tumors, lymphomas) with PC, thus cholesterol-lowering statins, vitamin D ana- suggesting a common genetic background. As logues. far as the role of androgen metabolism and an- drogen receptor (AR)-related genes in the devel- Key Words: opment of familial PC is concerned, a small Inheritance, Prostate cancer, Microenvironment, Tu- number of either guanine-guanine-cytosine (<16) mors, Urology. or cytosine-adenine-guanine (<18) repeats ap- pears to increase the AR activity, resulting in a raising PC risk. Regarding the expression of both androgen and estrogen receptor-related genes in sporadic and hereditary PC, the im- munohistochemistry findings show that the per- Introduction centage of AR-positive cancer cells is higher in hereditary PC than in sporadic forms, whereas In the developed Western countries, prostate the mean number of estrogen-α-receptor-posi- carcinoma (PC) is the most frequently diagnosed tive stromal cells is higher in sporadic PC rather α malignancy in men and the third most common than in that hereditary. As for 5- -steroid-reduc- cause of cancer-related mortality in North Amer- tase-2 gene, the dinucleotide thymine-adenine 1 repeated 18 times on the last exon, confers an ica . Its incidence and mortality vary consider- increased PC predisposition, as it is mainly ably among different ethnic groups, with high shown in African-American populations. Also prevalence in African-American men1,2. Corresponding Author: Contardo Alberti, MD; mobile: +39.331.9823032 31 C. Alberti Prostate carcinoma is a multifactorial disease predispose to it, likely interacting not only reci- whose etiology ranges from genetic factors to procally but also with environmental conditions, environmental conditions and internal microen- that, however, affect more strongly the sporadic vironment (“milieu intérieur”)3. Nevertheless, PC initiation4,9. after age and ethnic background, the strongest Hereditary transmission may be autosomal epidemiological risk factor for PC is a positive dominant – through the mother or the father – family history, several aggregation analyses and and even X-linked – through the mother to her linkage investigations showing that, on the one sons who will not transmit the susceptibility to hand, some alleles, with high penetrance, may their own sons –, and by the last way the disease confer a dominant inheritance susceptibility to jumping regularly one generation with subse- PC with rise in cases of the disease within indi- quent its under-estimation. Autosomal dominant vidual families (hereditary PC), and, on the oth- high-penetrant gene-related transmission is usu- er hand, many polymorphisms, with low pene- ally associated with disease onset at younger age trance, may influence, by integrating environ- while that recessive chromosome X-linked is mental conditions, the frequency of both familial characterized by late-onset disease4,8-10. and sporadic disease2,4-6. In this regard, a distinc- The first chromosome locus associated with tion must be made between hereditary and fa- hereditary PC was 1q24-25 and its putative gene milial forms, considering that hereditary trans- was named HPC1 (hereditary prostate carcinoma mission, compatible with Mendelian inheritance 1), which, in turn, was identified with RNaseL criteria, is demonstrated only in 5% of the cases gene (Table IA), involved in interferon-activated with PC family history whereas familial PC ac- apoptosis for virus-infected cells. Indeed, recent counts about 13-25% of cases. Indeed, families studies show that RNaseL gene mutations are re- with hereditary PC may be identified by having sponsible for PC particularly in men with γ-retro- three or more affected first-degree relatives (fa- virus-mediated prostate infections, among which ther, son, brother) within the nuclear family or, especially the xenotropic murine leukemia virus- differently, a frequency of PC in three successive related γ-retrovirus (XMRV). Actually, forty per- generations, or, at least, two affected relatives cent of hereditary PC patients homozigous for a before the age of 55 years4,6,7, given that genetic mutation in RNaseL are positive for XMRV susceptibility is proportionally more shown in whereas this virus is rarely detected in sporadic young patients rather than in old. Familial aggre- PC specimens, such finding meaning as a true gation of PC which don’t fulfill such criteria are breakthrough in the pathogenesis of PC. Poly- defined as familial forms, that, more properly, morphic variants within RNaseL gene are associ- are characterized by at least two affected first- ated with raised risk of hereditary PC4,8,10-12. degree relatives. Anyway, the risk of PC is about Other strong candidate susceptibility genes two-fold in the first-degree relatives of diseased are ElaC2/HPC2 (locus 17p11.2) and MSR1 men, it increasing proportionally to number of (macrophage scavenger receptor 1) (Table IA). diseased relatives and their decrease in age at the Also a mutation in a gene on 8q24 locus should diagnosis, so that the risk of developing a PC is appear to increase the risk of PC by 60%, but it assessed 8.5 for men with both first- and second- is more relevant to pathogenesis of familial and degree affected relatives4,6,8. sporadic PC. An indeterminate number of weak candidate susceptibility loci have been suggest- ed to be involved in hereditary PC (Table IB). Hereditary Form However, PC high risk alleles, that are able to drive a lifetime penetrance of at least 66%, have The definition of hereditary PC is mainly a frequency unlikely above 2-3% of the cases, based on the family history (pedigree). Despite whereas PC low risk alleles may have a more a strong support for a significant role of inherit- frequent impact on sporadic PC. With regard to ed genetic variants in PC etiopathogenesis, PC susceptibility locus 1q42.2-43 (PCAP, however few indisputable high-risk genetic ab- prostate cancer predisposing), the prostate carci- normalities have been shown in cases fulfilling noma tumor antigen-1 (PCTA-1), that is located the hereditary PC epidemiological criteria, thus within such chromosomal region, is not a PC suggesting that even the hereditary PC could be high risk gene while it could make one’s low a genetically heterogeneous disease. Many gene risk contribution to sporadic PC, but it must be loci rather than any major susceptibility gene throughly explored5,8,9,13. 32 Hereditary/familial versus sporadic prostate cancer Table I. Genes involved in hereditary PC. Gene Locus Encoding function Encoded protein A) Strong candidate susceptibility genes involved in hereditary prostate cancer • RNase L 1q24-25 Encodes RNaseL – RNaseL, endoribonuclease located (Ribonuclease L) HPC1 in cytoplasm and mithocondria. – Interferon-activated, it plays an antiviral and proapoptotic role • ElaC2 17p11.2 Encodes
Load more

Recommended publications
  • 502 the Keratinocyte Growth-Differentiation Switch Intact Skin
    [Frontiers in Bioscience 3, d502-508, May 15, 1998] THE KERATINOCYTE GROWTH-DIFFERENTIATION SWITCH Paolo Dotto Cutaneous Biology Research Center, Massachusetts General Hospital, Building 149, 13th Street, Charlestown, Massachusetts, 02129- 2000 Received 5/4/98 Accepted 5/8/98 TABLE OF CONTENTS 1. Abstract 2. Introduction 3. Signals which control the switch between keratinocyte growth and differentiation 4. Intermediate signalling pathways which are responsible for transduction of the differentiation signal 5. Tyrosine phosphorylation : key to regulation of keratinocyte differentiation 6. Transcription and cell cycle regulatory events connected with the onset of keratinocyte differentiation 7. References medium at low calcium concentrations (our unpublished 1. ABSTRACT observations). Growth/differentiation control of normal epithelial Besides calcium, growth/differentiation of primary cells has been relatively understudied, because of the keratinocyte cultures can be controlled by pharmacological complexities involved in their cultivation and means. In particular, treatment with the phorbol ester TPA characterization. The present review is focused on progress (12-0-tetradecanoylphorbol-13-acetate) induces growth in this area using the mouse primary keratinocyte system. arrest as well as expression of a set of differentiation This system reproduces under well defined culture markers such as involucrin, loricrin and filaggrin. However, conditions the switch between epithelial cell growth and expression of other markers induced differentiation
    [Show full text]
  • Interindividual Regulation of the BCRP/ABCG2 Transporter in Term Human Placentas
    DMD Fast Forward. Published on January 31, 2018 as DOI: 10.1124/dmd.117.079228 This article has not been copyedited and formatted. The final version may differ from this version. DMD #79228 Title Page Interindividual Regulation of the BCRP/ABCG2 Transporter in Term Human Placentas Kristin M Bircsak, Jamie E Moscovitz, Xia Wen, Faith Archer, Poi Yu Sofia Yuen, Moiz Mohammed, Naureen Memon, Barry I Weinberger, Laura M Saba, Anna M Vetrano, Lauren M Aleksunes Downloaded from Department of Pharmacology and Toxicology, Rutgers, The State University of New Jersey, Ernest Mario School of Pharmacy, Piscataway, NJ, USA (K.M.B., J.E.M., X.W., L.M.A.), dmd.aspetjournals.org Department of Pediatrics, Rutgers University Robert Wood Johnson Medical School, New Brunswick, NJ, USA (F.A., P.Y.S.Y, M.M., N.M., A.M.V.), Hofstra Northwell School of Medicine, Cohen Children’s Medical Center of New York, New Hyde Park, NY, USA (B.I.W.), at ASPET Journals on October 2, 2021 Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, CO, USA (L.S.), Environmental and Occupational Health Sciences Institute, Rutgers, The State University of New Jersey, Piscataway, NJ, USA (L.M.A.), Lipid Center, Rutgers, The State University of New Jersey, Piscataway, NJ, USA (L.M.A.) 1 DMD Fast Forward. Published on January 31, 2018 as DOI: 10.1124/dmd.117.079228 This article has not been copyedited and formatted. The final version may differ from this version. DMD #79228 Running Title Page Running title: Interindividual
    [Show full text]
  • Identification of Cigarette Smoke Condensate-Modulated Hiv-1-Associated Host Factors Using a Targeted Transcriptomic Approach
    Journal of HIV/AIDS & Infectious Diseases Research Open Access Identification of Cigarette Smoke Condensate-Modulated Hiv-1-Associated Host Factors Using A Targeted Transcriptomic Approach Janaki Purushe and Mario PS Chin* Department of Microbiology and Immunology, Center for Substance Abuse Research, Temple University School of Medicine, 3440 N. Broad Street, Philadelphia, PA 19140 *Corresponding author: Mario PS Chin, Department of Microbiology and Immunology, Center for Substance Abuse Research, Temple University School of Medicine, 3440 N. Broad Street, Philadelphia; E-mail: mpschin@ temple.edu Received Date: July 18, 2013, Accepted Date: September 13, 2013, Published Date: September 15, 2013 Citation: Mario PS Chin (2013) Identification of Cigarette Smoke Condensate-Modulated Hiv-1-Associated Host Factors Us- ing A Targeted Transcriptomic Approach. J HIV AIDS Infect Dis 1: 1-7. Abstract Tobacco use has been correlated with increased HIV-1 infection. In vitro characterization of alveolar macrophages obtained from uninfected cigarette smokers showed an increased susceptibility to HIV-1 infection when compared with cell from non-smokers. We showed that Cigarette Smoke Condensate (CSC) enhances HIV-1 infection in primary CD4+ cells. The underlying mechanisms of how CSC affects HIV-1 replication are unclear. The traditional approach that studies the specific cellular processes that are modulated by CSC and examines the resulting effects on viral replication has generated incon- clusive results. Indeed, CSC has a pleiotropic effect on cell expression and transcriptomic studies have shown that CSC can modulate the expression of a large number of genes. This global transcriptomic approach generates a large number of unreg- ulated and downregulated genes, prohibiting the specific functional analysis of genes that are related to viral replication.
    [Show full text]
  • Sp1 Transcription Factor: a Long-Standing Target in Cancer Chemotherapy
    Sp1 transcription factor: A long-standing target in cancer chemotherapy Carolina Vizcaíno, Sylvia Mansilla and José Portugal* Instituto de Biología Molecular de Barcelona, CSIC, Parc Científic de Barcelona, E-08028 Barcelona, Spain *to whom correspondence should be addressed: Dr. José Portugal, Instituto de Biología Molecular de Barcelona, CSIC, Parc Científic de Barcelona, Baldiri Reixac, 10; E-08028 Barcelona, Spain. Phone: +34 93 403 4959, FAX: +34 93 403 4979, E-mail: [email protected] 1 ABSTRACT Sp1 (Specificity protein 1) is a well-known member of a family of transcription factors that also includes Sp2, Sp3 and Sp4, which are implicated in an ample variety of essential biological processes and have been proven important in cell growth, differentiation, apoptosis and carcinogenesis. Sp1 activates the transcription of many cellular genes that contain putative CG- rich Sp-binding sites in their promoters. Sp1 and Sp3 proteins bind to similar, if not the same, DNA tracts and compete for binding, thus they can enhance or repress gene expression. Evidences exist that the Sp-family of proteins regulates the expression of genes that play pivotal roles in cell proliferation and metastasis of various tumors. In patients with a variety of cancers, high levels of Sp1 protein are considered a negative prognostic factor. A plethora of compounds can interfere with the trans-activating activities of Sp1 and other Sp proteins on gene expression. Several pathways are involved in the down-regulation of Sp proteins by compounds with different mechanisms of action, which include not only the direct interference with the binding of Sp proteins to their putative DNA binding sites, but also promoting the degradation of Sp protein factors.
    [Show full text]
  • Interindividual Regulation of the BCRP/ABCG2 Transporter in Term Human Placentas
    DMD Fast Forward. Published on January 31, 2018 as DOI: 10.1124/dmd.117.079228 This article has not been copyedited and formatted. The final version may differ from this version. DMD #79228 Title Page Interindividual Regulation of the BCRP/ABCG2 Transporter in Term Human Placentas Kristin M Bircsak, Jamie E Moscovitz, Xia Wen, Faith Archer, Poi Yu Sofia Yuen, Moiz Mohammed, Naureen Memon, Barry I Weinberger, Laura M Saba, Anna M Vetrano, Lauren M Aleksunes Downloaded from Department of Pharmacology and Toxicology, Rutgers, The State University of New Jersey, Ernest Mario School of Pharmacy, Piscataway, NJ, USA (K.M.B., J.E.M., X.W., L.M.A.), dmd.aspetjournals.org Department of Pediatrics, Rutgers University Robert Wood Johnson Medical School, New Brunswick, NJ, USA (F.A., P.Y.S.Y, M.M., N.M., A.M.V.), Hofstra Northwell School of Medicine, Cohen Children’s Medical Center of New York, New Hyde Park, NY, USA (B.I.W.), at ASPET Journals on October 1, 2021 Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, CO, USA (L.S.), Environmental and Occupational Health Sciences Institute, Rutgers, The State University of New Jersey, Piscataway, NJ, USA (L.M.A.), Lipid Center, Rutgers, The State University of New Jersey, Piscataway, NJ, USA (L.M.A.) 1 DMD Fast Forward. Published on January 31, 2018 as DOI: 10.1124/dmd.117.079228 This article has not been copyedited and formatted. The final version may differ from this version. DMD #79228 Running Title Page Running title: Interindividual
    [Show full text]
  • Supplementary Table 1A. Genes Significantly Altered in A4573 ESFT
    Supplementary Table 1A. Genes significantly altered in A4573 ESFT cells following BMI-1knockdown genesymbol genedescription siControl siBMI1 FC Direction P-value AASS aminoadipate-semialdehyde synthase | tetra-peptide repeat homeobox-like6.68 7.24 1.5 Up 0.007 ABCA2 ATP-binding cassette, sub-family A (ABC1), member 2 | neural5.44 proliferation,6.3 differentiation1.8 and Upcontrol, 1 0.006 ABHD4 abhydrolase domain containing 4 7.51 6.69 1.8 Down 0.002 ACACA acetyl-Coenzyme A carboxylase alpha | peroxiredoxin 5 | similar6.2 to High mobility7.26 group2.1 protein UpB1 (High mobility0.009 group protein 1) (HMG-1) (Amphoterin) (Heparin-binding protein p30) | Coenzyme A synthase ACAD9 acyl-Coenzyme A dehydrogenase family, member 9 9.25 8.59 1.6 Down 0.008 ACBD3 acyl-Coenzyme A binding domain containing 3 7.89 8.53 1.6 Up 0.008 ACCN2 amiloride-sensitive cation channel 2, neuronal 5.47 6.28 1.8 Up 0.005 ACIN1 apoptotic chromatin condensation inducer 1 7.15 7.79 1.6 Up 0.008 ACPL2 acid phosphatase-like 2 6.04 7.6 2.9 Up 0.000 ACSL4 acyl-CoA synthetase long-chain family member 4 6.72 5.8 1.9 Down 0.001 ACTA2 actin, alpha 2, smooth muscle, aorta 9.18 8.44 1.7 Down 0.003 ACYP1 acylphosphatase 1, erythrocyte (common) type 7.09 7.66 1.5 Up 0.009 ADA adenosine deaminase 6.34 7.1 1.7 Up 0.009 ADAL adenosine deaminase-like 7.88 6.89 2.0 Down 0.006 ADAMTS1 ADAM metallopeptidase with thrombospondin type 1 motif, 1 6.57 7.65 2.1 Up 0.000 ADARB1 adenosine deaminase, RNA-specific, B1 (RED1 homolog rat) 6.49 7.13 1.6 Up 0.008 ADCY9 adenylate cyclase 9 6.5 7.18
    [Show full text]
  • Ab207227 Sp1/Sp3 Transcription Factor Assay Kit (Colorimetric)
    ab207227 Sp1/Sp3 Transcription Factor Assay Kit (Colorimetric) Instructions for use: For quantitative measurement of Sp1/Sp3 Activation in human, mouse and rat nuclear extracts. This product is for research use only and is not intended for diagnostic use. Version 2 Last Updated 24 August 2017 Table of Contents INTRODUCTION 1 1. BACKGROUND 1 2. ASSAY SUMMARY 3 GENERAL INFORMATION 4 3. PRECAUTIONS 4 4. STORAGE AND STABILITY 4 5. LIMITATIONS 5 6. MATERIALS SUPPLIED 5 7. MATERIALS REQUIRED, NOT SUPPLIED 6 8. TECHNICAL HINTS 7 ASSAY PREPARATION 8 9. REAGENT PREPARATION 8 10. SAMPLE PREPARATION 14 ASSAY PROCEDURE 16 11. ASSAY PROCEDURE 16 DATA ANALYSIS 18 12. TYPICAL DATA 18 RESOURCES 19 13. QUICK ASSAY PROCEDURE 19 14. TROUBLESHOOTING 20 15. INTERFERENCES 21 16. NOTES 22 INTRODUCTION INTRODUCTION 1. BACKGROUND Sp1/Sp3 Transcription Factor Assay Kit (Colorimetric) (ab207227) is a high throughput assay to quantify Sp1/Sp3 activation. This assay combines a quick ELISA format with a sensitive and specific non- radioactive assay for transcription factor activation. A specific double stranded DNA sequence containing the Sp1/Sp3 consensus binding site (5’ – GGGGCGGGG – 3’) has been immobilized onto a 96-well plate. Active Sp1/Sp3 present in the nuclear extract specifically binds to the oligonucleotide. Sp1/Sp3 is detected by a primary antibody that recognizes an epitope of Sp1/Sp3 accessible only when the protein is activated and bound to its target DNA. An HRP- conjugated secondary antibody provides sensitive colorimetric readout at OD 450 nm. This product detects human, mouse and rat Sp1/Sp3. Key performance and benefits: Assay time: 3.5 hours (cell extracts preparation not included).
    [Show full text]
  • Keep Your Fingers Off My DNA: Protein-Protein Interactions
    1 2 Keep your fingers off my DNA: 3 protein-protein interactions mediated by C2H2 zinc finger domains 4 5 6 a scholarly review 7 8 9 10 11 Kathryn J. Brayer1 and David J. Segal2* 12 13 14 15 16 17 1Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, 18 Tucson, AZ, 85721. 19 2Genome Center and Department of Pharmacology, University of California, Davis, CA, 95616. 20 21 22 23 24 *To whom correspondence should be addressed: 25 David J. Segal, Ph.D. 26 University of California, Davis 27 Genome Center/Pharmacology 28 4513 GBSF 29 451 E. Health Sciences Dr. 30 Davis, CA 95616 31 Tel: 530-754-9134 32 Fax: 530-754-9658 33 Email: [email protected] 34 35 36 Running header: C2H2 ZF interactions with proteins 37 38 Keywords: transcription factors, protein-DNA interactions, protein chemistry, structural biology, 39 functional annotations 40 41 Abstract: 154 words 42 Body Text: 5863 words 43 Figures: 9 44 Tables: 5 45 References: 165 46 C2H2 ZF interactions with proteins Brayer and Segal - review 46 ABSTRACT 47 Cys2-His2 (C2H2) zinc finger domains were originally identified as DNA binding 48 domains, and uncharacterized domains are typically assumed to function in DNA binding. 49 However, a growing body of evidence suggests an important and widespread role for these 50 domains in protein binding. There are even examples of zinc fingers that support both DNA and 51 protein interactions, which can be found in well-known DNA-binding proteins such as Sp1, 52 Zif268, and YY1. C2H2 protein-protein interactions are proving to be more abundant than 53 previously appreciated, more plastic than their DNA-binding counterparts, and more variable and 54 complex in their interactions surfaces.
    [Show full text]
  • Comprehensive Biological Information Analysis of PTEN Gene in Pan-Cancer
    Comprehensive biological information analysis of PTEN gene in pan-cancer Hang Zhang Shanghai Medical University: Fudan University https://orcid.org/0000-0002-5853-7754 Wenhan Zhou Shanghai Medical University: Fudan University Xiaoyi Yang Shanghai Jiao Tong University School of Medicine Shuzhan Wen Shanghai Medical University: Fudan University Baicheng Zhao Shanghai Medical University: Fudan University Jiale Feng Shanghai Medical University: Fudan University Shuying Chen ( [email protected] ) https://orcid.org/0000-0002-9215-9777 Primary research Keywords: PTEN, correlated genes, TCGA, GEPIA, UALCAN, GTEx, expression, cancer Posted Date: April 12th, 2021 DOI: https://doi.org/10.21203/rs.3.rs-388887/v1 License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License Page 1/21 Abstract Background PTEN is a multifunctional tumor suppressor gene mutating at high frequency in a variety of cancers. However, its expression in pan-cancer, correlated genes, survival prognosis, and regulatory pathways are not completely described. Here, we aimed to conduct a comprehensive analysis from the above perspectives in order to provide reference for clinical application. Methods we studied the expression levels in cancers by using data from TCGA and GTEx database. Obtain expression box plot from UALCAN database. Perform mutation analysis on the cBioportal website. Obtain correlation genes on the GEPIA website. Construct protein network and perform KEGG and GO enrichment analysis on the STRING database. Perform prognostic analysis on the Kaplan-Meier Plotter website. We also performed transcription factor prediction on the PROMO database and performed RNA-RNA association and RNA-protein interaction on the RNAup Web server and RPISEq.
    [Show full text]
  • 1 SUPPLEMENTAL DATA Figure S1. Poly I:C Induces IFN-Β Expression
    SUPPLEMENTAL DATA Figure S1. Poly I:C induces IFN-β expression and signaling. Fibroblasts were incubated in media with or without Poly I:C for 24 h. RNA was isolated and processed for microarray analysis. Genes showing >2-fold up- or down-regulation compared to control fibroblasts were analyzed using Ingenuity Pathway Analysis Software (Red color, up-regulation; Green color, down-regulation). The transcripts with known gene identifiers (HUGO gene symbols) were entered into the Ingenuity Pathways Knowledge Base IPA 4.0. Each gene identifier mapped in the Ingenuity Pathways Knowledge Base was termed as a focus gene, which was overlaid into a global molecular network established from the information in the Ingenuity Pathways Knowledge Base. Each network contained a maximum of 35 focus genes. 1 Figure S2. The overlap of genes regulated by Poly I:C and by IFN. Bioinformatics analysis was conducted to generate a list of 2003 genes showing >2 fold up or down- regulation in fibroblasts treated with Poly I:C for 24 h. The overlap of this gene set with the 117 skin gene IFN Core Signature comprised of datasets of skin cells stimulated by IFN (Wong et al, 2012) was generated using Microsoft Excel. 2 Symbol Description polyIC 24h IFN 24h CXCL10 chemokine (C-X-C motif) ligand 10 129 7.14 CCL5 chemokine (C-C motif) ligand 5 118 1.12 CCL5 chemokine (C-C motif) ligand 5 115 1.01 OASL 2'-5'-oligoadenylate synthetase-like 83.3 9.52 CCL8 chemokine (C-C motif) ligand 8 78.5 3.25 IDO1 indoleamine 2,3-dioxygenase 1 76.3 3.5 IFI27 interferon, alpha-inducible
    [Show full text]
  • The Role of NF-Y in the Transcriptional Regulation of Human Topoisomerase II
    Copyright is owned by the Author of the thesis. Permission is given for a copy to be downloaded by an individual for the purpose of research and private study only. The thesis may not be reproduced elsewhere without the permission of the Author. The Role of NF-Y in the Transcriptional Regulation of Human Topoisomerase Ila A thesis presented to Massey University in partial fulfilment of the requirement for the degree of Master of Science in Biochemistry Patricia Ann Hintz 2001 ACKNOWLEDGEMENTS First of all, I would like to thank my very patient and wonderful supervisor Dr Kathryn Stowell for her support, enthusiasm, expertise, and for giving me the opportunity to be challenged and involved in a very interesting research project. I would also like to take this opportunity to thank the various and varied members of the Twilight Zone particularly Carole Flyger, Kirsty Allen and Angela Jones for their friendship, advice and support during the course of this study. I would also like to thank my parents, Geoffrey and Adrienne Hintz, and my sister Carolyn for their everlasting love, support and understanding. Finally, I would like to thank Dwayne, without you, none of what I have done or still might do would be possible. .1 ABSTRACT DNA topoisomerases are ubiquitous enzymes that catalyse reactions that alter the topological state of DNA during the various processes of DNA metabolism including transcription, recombination, replication and chromosome segregation. Human cells exhibit a Type II enzyme termed DNA topoisomerase Ila. This enzyme is expressed at higher levels in proliferating cells due to an increased demand for chromosome separation.
    [Show full text]
  • Cdc25b Is Negatively Regulated by P53 Through Sp1 and NF-Y Transcription Factors
    Oncogene (2011) 30, 2282–2288 & 2011 Macmillan Publishers Limited All rights reserved 0950-9232/11 www.nature.com/onc SHORT COMMUNICATION Cdc25B is negatively regulated by p53 through Sp1 and NF-Y transcription factors M Dalvai1,2,5, O Mondesert1,2, J-C Bourdon3, B Ducommun1,2,4 and C Dozier1,2 1Universite´ de Toulouse, LBCMCP, Toulouse, France; 2CNRS, LBCMCP—UMR 5088 CNRS, University of Toulouse, Toulouse, France; 3Inserm-European Associated Laboratory U858, Department of Surgery and Molecular Oncology, College of Medicine, University of Dundee, Dundee, UK and 4CHU de Toulouse, Toulouse, France Cdc25B phosphatases function as key players in G2/M CDK–cyclin complexes (Boutros et al., 2006). Cdc25B is cell cycle progression by activating the CDK1–cyclinB1 thought to act as the starter of mitosis, being responsible complexes. They also have an essential role in recovery for the initial dephosphorylation and activation of the from the G2/M checkpoint activated in response to DNA CDK1–cyclinB1 complex (Lindqvist et al., 2005). damage. Overexpression of Cdc25B results in bypass of Cdc25B is also essential for cell cycle recovery after the G2/M checkpoint and illegitimate entry into mitosis, DNA-damage induced checkpoint and its overexpres- and also causes replicative stress, leading to genomic sion results in bypass of the G2/M checkpoint and instability. Thus, fine-tuning of Cdc25B expression level illegitimate entry into mitosis, and also causes replica- is critical for correct cell cycle progression and G2 tive stress, leading to genomic instability (Miyata et al., checkpoint recovery. However, the transcriptional regula- 2001; Bugler et al., 2006). Thus, fine-tuning of Cdc25B tion of Cdc25B remains largely unknown.
    [Show full text]