DOCSLIB.ORG

Growth and Gene Expression Profile Analyses of Endometrial Cancer Cells Expressing Exogenous PTEN

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Growth and Gene Expression Profile Analyses of Endometrial Cancer Cells Expressing Exogenous PTEN [CANCER RESEARCH 61, 3741–3749, May 1, 2001] Growth and Gene Expression Profile Analyses of Endometrial Cancer Cells Expressing Exogenous PTEN Mieko Matsushima-Nishiu, Motoko Unoki, Kenji Ono, Tatsuhiko Tsunoda, Takeo Minaguchi, Hiroyuki Kuramoto, Masato Nishida, Toyomi Satoh, Toshihiro Tanaka, and Yusuke Nakamura1 Laboratories of Molecular Medicine [M. M-N., M. U., K. O., T. M., T. Ta., Y. N.] and Genome Database [T. Ts.], Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan; Department of Obstetrics and Gynecology, School of Medicine, Kitasato University, Sagamihara 228-8555, Japan [H. K.]; Department of Obstetrics and Gynecology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba 305-8576, Japan [M. N.]; and Department of Obstetrics and Gynecology, Ibaraki Seinan Central Hospital, Tsukuba 306-0433, Japan [T. S.] ABSTRACT Akt/protein kinase B, cell survival, and cell proliferation (8). Over- expression of PTEN can decrease cell proliferation and tumorigenicity The PTEN tumor suppressor gene encodes a multifunctional phospha- (9, 10), an observation attributed to the ability of PTEN to induce cell tase that plays an important role in inhibiting the phosphatidylinositol-3- cycle arrest and apoptosis (11, 12). kinase pathway and downstream functions that include activation of Akt/protein kinase B, cell survival, and cell proliferation. Enforced ex- Thus, lack of PTEN expression may affect a complex set of pression of PTEN in various cancer cell lines decreases cell proliferation transcriptional targets. However, no systematic assessment of PTEN- through arrest of the cell cycle, accompanied in some cases by induction regulated targets in cancer cells has been reported to date. We used a of apoptosis. We used cDNA microarrays containing 4009 cDNAs to cDNA microarray to investigate transcriptional changes related to examine changes in gene-expression profiles when exogenous PTEN was PTEN signaling or secondary changes caused by the initiation of induced in PTEN-defective cells. The microarrays and subsequent semi- apoptosis or cell cycle arrest by transfecting wild-type PTEN into quantitative reverse transcription-PCR analysis revealed transcriptional cancer cells that were deficient in endogenous PTEN. Microarray stimulation of 99 genes and repression of 72 genes. Some of the differen- technology, which can permit analysis of the expression of thousands tially expressed genes already had been implicated in cell proliferation, of genes simultaneously, is a proven method for investigating gene- differentiation, apoptosis, or cell cycle control, e.g., overexpression of expression profiles in human cancers (13, 14). PTEN-induced transactivation of cyclin-dependent inhibitor 1B (p27Kip1) and 2B (p15INK4B), members of the TNF receptor family, tumor necrosis factor-associated genes, and members of the Notch-signaling and Mad families. To our knowledge this is the first report of transactivation of MATERIALS AND METHODS those genes by PTEN. The genes differentially expressed in our experi- Cell Culture. The 14 endometrial cancer cell lines used in this study are ments also included many whose correlation with cancer development had described in Table 1. Ishikawa3-H-12 (15, 16) was obtained from Tsukuba not been recognized before. Our data should contribute to a greater University (Tsukuba, Japan). HEC-1 (17), HEC-6 (18), HEC-50 (19), HEC59 understanding of the broad spectrum of ways in which PTEN affects (20), HEC-88 (20), HEC-108 (20), HEC-116 (20), and HEC-151 (21) were intracellular signaling pathways. Analysis of expression profiles with mi- obtained from Kitasato University (Sagamihara, Japan). AN3CA and KLE croarrays appears to be a powerful approach for identifying anticancer were obtained from the American Type Culture Collection (Manassas, VA), genes and/or disease-specific targets for cancer therapy. and Sawano (22), HHUA, and HOUA-I were obtained from the RIKEN Gene Bank (Tsukuba, Japan). Ishikawa3-H-12, Sawano, HEC-1, HEC-6, HEC-50, HEC59, HEC-88, HEC-108, HEC-116, HEC-151, and AN3CA cells were INTRODUCTION maintained in Eagle’s MEM with 10% FBS. HHUA and HOUA-I cells were The PTEN/MMAC12 gene on chromosome 10q23.3 has been iden- grown in Ham’s F12 medium with 10% FBS. KLE cells were grown in 1:1 tified as a tumor suppressor (1, 2). Deletions and mutations in PTEN mixture of DMEM and Ham’s F12 medium with 10% FBS. DNA Extraction and Mutation Screening. Genomic DNA was extracted occur frequently in advanced carcinomas of endometrium, breast, from each cell line using standard methods. All nine coding exons of PTEN bladder, and endometrioid ovarian tissue and also in glioblastomas were amplified from these DNA samples, and their nucleotide sequences were and malignant melanomas (1–4). Germ-line mutations of PTEN are determined by direct sequencing using BigDye Terminator RR Mix (Applied the cause of Cowden’s and Bannayan-Zonana syndromes of cancer Biosystems, Foster City, CA) on an ABI model 3700 DNA sequencer (Applied predisposition (5, 6). Biosystems) to reveal any mutations in the PTEN gene. A recent study demonstrated that PTEN acts as a phospholipid Construction of Recombinant Adenovirus. To construct AdCAPTEN phosphatase dephosphorylating the PtdIns (3,4,5)P3 and PtdIns viral vectors, the cDNA of PTEN was cloned by RT-PCR using placental (3,4)P2, resulting in PtdIns (4,5)P2 and PtdIns (4)P, respectively (7). mRNA as a template and primers 5Ј-CTT CAGCCACAGGCTCCCA-3Ј and It modulates the PI3K pathway by catalyzing degradation of the 5Ј-TGGTGTTTTATCCCTCTTGATA-3Ј. A 1.2-kb fragment of PTEN cDNA PtdIns (3,4,5)P3 generated by PI3K. This mechanism inhibits down- was cloned into the SwaI site of cosmid pAxCAwt (TaKaRa; Ref. 23), which contains the CAG promoter (composed of the cytomegalovirus enhancer and stream functions mediated by the PI3K pathway, such as activation of chicken ␤-actin promoter; Ref. 24) and an entire genome of type 5 adenovirus except for the E1 and E3 regions. Recombinant adenoviruses were constructed Received 4/27/00; accepted 2/28/01. by in vitro homologous recombination in the human embryonic kidney (HEK) The costs of publication of this article were defrayed in part by the payment of page cell line 293, using pAxCAPTEN and the adenovirus DNA terminal-protein charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. complex (TaKaRa; Ref. 23). As a control, AdCA viruses were generated from 1 To whom requests for reprints should be addressed, at Laboratory of Molecular cosmid pAxCAwt without a transgene. AdCALacZ viruses encoding the ␤-gal Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, gene under the control of the CAG promoter were constructed from the control 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan. Phone: 81-3-5449-5372; Fax: cosmid pAxCALacZ (TaKaRa). Viruses were propagated in the HEK293 cell 81-3-5449-5433; E-mail: [email protected]. 2 The abbreviations used are: PTEN, phosphatase and tensin homologue deleted on line and purified by two rounds of CsCl density centrifugation; viral titers were chromosome 10; MMAC1, mutated in multiple advanced cancers 1; PtdIns, phosphati- measured in a limiting-dilution bioassay using the HEK293 cells. In this study, dylinositol; P3, triphosphate; P2, biphosphate; PI3K, phosphatidylinositol-3-kinase; FBS, we used recombinant adenovirus stocks of fewer than five passages to mini- ␤ ␤ fetal bovine serum; MOI, multiplicity of infection; -gal, -galactosidase; MTT, 3, mize the possibility of replication-competent adenovirus contamination. (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; TUNEL, terminal de- ␤ oxynucleotidyl transferase-mediated nick end labeling; RT-PCR, reverse transcription- -Galactosidase Transduction Assay. To assess efficiency of adenovirus- PCR; TNF, tumor necrosis factor; PI, propidium iodide. mediated gene transfer, 1 ϫ 105 cells from each culture were plated in 3741 Downloaded from cancerres.aacrjournals.org on September 26, 2021. © 2001 American Association for Cancer Research. GENE EXPRESSION PROFILES IN PTEN-TRANSFECTED CELLS Table 1 Characteristics of endometrial cancer cell lines (PTEN status and transduction efficiency) PTEN statusa Transduction efficiency (%)b Cell line Codon Mutation Predicted effect MOI 20 MOI 100 Sourcec HHUA 164 1bp(A) del Frameshift 48.2 89.7 1 289 1bp(A) del Frameshift HOUA-1 267 1bp(A) ins Frameshift 44.4 94.8 1 289 1bp(A) ins Frameshift Ishikawa 3-H-12 289 1bp(A) del Frameshift 66.5 100.0 2 317–318 4bp(ACTT) del Frameshift Sawano 16 2bp(AT) del Frameshift 27 94.8 2 130 CGA to GGA Arg(R) to Gly(G) HEC-1 None 79.3 100.0 3 HEC-6 intron 4(ϩ2) T to C Splice donor 44 79.5 3 289 1bp(A) del Frameshift HEC-50 None 43.5 100 3 HEC-59 41 TAC to CAC Tyr(Y) to His(H) 68.3 100.0 3 233 CGA to TGA Stop 246 CCG to CTG Pro(P) to Leu(L) 267 1bp(A) del Frameshift HEC-88 130 CGA to GGA Arg(R) to Gly(G) 95.5 100.0 3 173 CGC to TGC Arg(R) to Cys(C) 310 GAT to TAT Asp(D) to Tyr(Y) 341 TTT to TGT Phe(F) to Cys(C) HEC-108 6 2bp(AA) del Frameshift 66.7 100.0 3 289 1bp(A) del Frameshift HEC-116 Intron 2(Ϫ1) G to A Splice acceptor 57.6 100.0 3 173 CGC to TGC Arg(R) to Cys(C) 233 CGA to TGA Stop HEC-151 33 3bp(ATT) del In-frame deletion 78 100.0 3 76 2bp(AT) del Frameshift AN3CA 130 1bp(G) del Frameshift 0.9 5.3 4 KLE None 66.3 97.3 4 a PTEN mutations were detected by DNA sequencing. b Percentage of ␤-gal-positive cells 24 h after infection with AdCALacZ.
Load more

Recommended publications
  • Screening and Identification of Key Biomarkers in Clear Cell Renal Cell Carcinoma Based on Bioinformatics Analysis
    bioRxiv preprint doi: https://doi.org/10.1101/2020.12.21.423889; this version posted December 23, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Screening and identification of key biomarkers in clear cell renal cell carcinoma based on bioinformatics analysis Basavaraj Vastrad1, Chanabasayya Vastrad*2 , Iranna Kotturshetti 1. Department of Biochemistry, Basaveshwar College of Pharmacy, Gadag, Karnataka 582103, India. 2. Biostatistics and Bioinformatics, Chanabasava Nilaya, Bharthinagar, Dharwad 580001, Karanataka, India. 3. Department of Ayurveda, Rajiv Gandhi Education Society`s Ayurvedic Medical College, Ron, Karnataka 562209, India. * Chanabasayya Vastrad [email protected] Ph: +919480073398 Chanabasava Nilaya, Bharthinagar, Dharwad 580001 , Karanataka, India bioRxiv preprint doi: https://doi.org/10.1101/2020.12.21.423889; this version posted December 23, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Abstract Clear cell renal cell carcinoma (ccRCC) is one of the most common types of malignancy of the urinary system. The pathogenesis and effective diagnosis of ccRCC have become popular topics for research in the previous decade. In the current study, an integrated bioinformatics analysis was performed to identify core genes associated in ccRCC. An expression dataset (GSE105261) was downloaded from the Gene Expression Omnibus database, and included 26 ccRCC and 9 normal kideny samples. Assessment of the microarray dataset led to the recognition of differentially expressed genes (DEGs), which was subsequently used for pathway and gene ontology (GO) enrichment analysis.
    [Show full text]
  • Supplement 1 Overview of Dystonia Genes
    Supplement 1 Overview of genes that may cause dystonia in children and adolescents Gene (OMIM) Disease name/phenotype Mode of inheritance 1: (Formerly called) Primary dystonias (DYTs): TOR1A (605204) DYT1: Early-onset generalized AD primary torsion dystonia (PTD) TUBB4A (602662) DYT4: Whispering dystonia AD GCH1 (600225) DYT5: GTP-cyclohydrolase 1 AD deficiency THAP1 (609520) DYT6: Adolescent onset torsion AD dystonia, mixed type PNKD/MR1 (609023) DYT8: Paroxysmal non- AD kinesigenic dyskinesia SLC2A1 (138140) DYT9/18: Paroxysmal choreoathetosis with episodic AD ataxia and spasticity/GLUT1 deficiency syndrome-1 PRRT2 (614386) DYT10: Paroxysmal kinesigenic AD dyskinesia SGCE (604149) DYT11: Myoclonus-dystonia AD ATP1A3 (182350) DYT12: Rapid-onset dystonia AD parkinsonism PRKRA (603424) DYT16: Young-onset dystonia AR parkinsonism ANO3 (610110) DYT24: Primary focal dystonia AD GNAL (139312) DYT25: Primary torsion dystonia AD 2: Inborn errors of metabolism: GCDH (608801) Glutaric aciduria type 1 AR PCCA (232000) Propionic aciduria AR PCCB (232050) Propionic aciduria AR MUT (609058) Methylmalonic aciduria AR MMAA (607481) Cobalamin A deficiency AR MMAB (607568) Cobalamin B deficiency AR MMACHC (609831) Cobalamin C deficiency AR C2orf25 (611935) Cobalamin D deficiency AR MTRR (602568) Cobalamin E deficiency AR LMBRD1 (612625) Cobalamin F deficiency AR MTR (156570) Cobalamin G deficiency AR CBS (613381) Homocysteinuria AR PCBD (126090) Hyperphelaninemia variant D AR TH (191290) Tyrosine hydroxylase deficiency AR SPR (182125) Sepiaterine reductase
    [Show full text]
  • Molecular and Physiological Basis for Hair Loss in Near Naked Hairless and Oak Ridge Rhino-Like Mouse Models: Tracking the Role of the Hairless Gene
    University of Tennessee, Knoxville TRACE: Tennessee Research and Creative Exchange Doctoral Dissertations Graduate School 5-2006 Molecular and Physiological Basis for Hair Loss in Near Naked Hairless and Oak Ridge Rhino-like Mouse Models: Tracking the Role of the Hairless Gene Yutao Liu University of Tennessee - Knoxville Follow this and additional works at: https://trace.tennessee.edu/utk_graddiss Part of the Life Sciences Commons Recommended Citation Liu, Yutao, "Molecular and Physiological Basis for Hair Loss in Near Naked Hairless and Oak Ridge Rhino- like Mouse Models: Tracking the Role of the Hairless Gene. " PhD diss., University of Tennessee, 2006. https://trace.tennessee.edu/utk_graddiss/1824 This Dissertation is brought to you for free and open access by the Graduate School at TRACE: Tennessee Research and Creative Exchange. It has been accepted for inclusion in Doctoral Dissertations by an authorized administrator of TRACE: Tennessee Research and Creative Exchange. For more information, please contact [email protected]. To the Graduate Council: I am submitting herewith a dissertation written by Yutao Liu entitled "Molecular and Physiological Basis for Hair Loss in Near Naked Hairless and Oak Ridge Rhino-like Mouse Models: Tracking the Role of the Hairless Gene." I have examined the final electronic copy of this dissertation for form and content and recommend that it be accepted in partial fulfillment of the requirements for the degree of Doctor of Philosophy, with a major in Life Sciences. Brynn H. Voy, Major Professor We have read this dissertation and recommend its acceptance: Naima Moustaid-Moussa, Yisong Wang, Rogert Hettich Accepted for the Council: Carolyn R.
    [Show full text]
  • Assessment of a Targeted Gene Panel for Identification of Genes Associated with Movement Disorders
    Supplementary Online Content Montaut S, Tranchant C, Drouot N, et al; French Parkinson’s and Movement Disorders Consortium. Assessment of a targeted gene panel for identification of genes associated with movement disorders. JAMA Neurol. Published online June 18, 2018. doi:10.1001/jamaneurol.2018.1478 eMethods. Supplemental methods. eTable 1. Name, phenotype and inheritance of the genes included in the panel. eTable 2. Probable pathogenic variants identified in a cohort of 23 patients with cerebellar ataxia using WES analysis. eTable 3. Negative cases in a cohort of 23 patients with cerebellar ataxia studied using WES analysis. eTable 4. Variants of unknown significance (VUSs) identified in the cohort. eFigure 1. Examples of pedigrees of cases with identified causative variants. eFigure 2. Pedigrees suggesting mendelian inheritance in negative cases. eFigure 3. Examples of pedigrees of cases with identified VUSs. eResults. Supplemental results. This supplementary material has been provided by the authors to give readers additional information about their work. © 2018 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/26/2021 eMethods. Supplemental methods Patients selection In the multicentric, prospective study, patients were selected from 25 French, 1 Luxembourg and 1 Algerian tertiary MDs centers between September 2014 and July 2016. Inclusion criteria were patients (1) who had developed one or several chronic MDs (2) with an age of onset below 40 years and/or presence of a family history of MDs. Patients suffering from essential tremor, tic or Gilles de la Tourette syndrome, pure cerebellar ataxia or with clinical/paraclinical findings suggestive of an acquired cause were excluded.
    [Show full text]
  • RNA Epigenetics: Fine-Tuning Chromatin Plasticity and Transcriptional Regulation, and the Implications in Human Diseases
    G C A T T A C G G C A T genes Review RNA Epigenetics: Fine-Tuning Chromatin Plasticity and Transcriptional Regulation, and the Implications in Human Diseases Amber Willbanks, Shaun Wood and Jason X. Cheng * Department of Pathology, Hematopathology Section, University of Chicago, Chicago, IL 60637, USA; [email protected] (A.W.); [email protected] (S.W.) * Correspondence: [email protected] Abstract: Chromatin structure plays an essential role in eukaryotic gene expression and cell identity. Traditionally, DNA and histone modifications have been the focus of chromatin regulation; however, recent molecular and imaging studies have revealed an intimate connection between RNA epigenetics and chromatin structure. Accumulating evidence suggests that RNA serves as the interplay between chromatin and the transcription and splicing machineries within the cell. Additionally, epigenetic modifications of nascent RNAs fine-tune these interactions to regulate gene expression at the co- and post-transcriptional levels in normal cell development and human diseases. This review will provide an overview of recent advances in the emerging field of RNA epigenetics, specifically the role of RNA modifications and RNA modifying proteins in chromatin remodeling, transcription activation and RNA processing, as well as translational implications in human diseases. Keywords: 5’ cap (5’ cap); 7-methylguanosine (m7G); R-loops; N6-methyladenosine (m6A); RNA editing; A-to-I; C-to-U; 2’-O-methylation (Nm); 5-methylcytosine (m5C); NOL1/NOP2/sun domain Citation: Willbanks, A.; Wood, S.; (NSUN); MYC Cheng, J.X. RNA Epigenetics: Fine-Tuning Chromatin Plasticity and Transcriptional Regulation, and the Implications in Human Diseases. Genes 2021, 12, 627.
    [Show full text]
  • 1 Metabolic Dysfunction Is Restricted to the Sciatic Nerve in Experimental
    Page 1 of 255 Diabetes Metabolic dysfunction is restricted to the sciatic nerve in experimental diabetic neuropathy Oliver J. Freeman1,2, Richard D. Unwin2,3, Andrew W. Dowsey2,3, Paul Begley2,3, Sumia Ali1, Katherine A. Hollywood2,3, Nitin Rustogi2,3, Rasmus S. Petersen1, Warwick B. Dunn2,3†, Garth J.S. Cooper2,3,4,5* & Natalie J. Gardiner1* 1 Faculty of Life Sciences, University of Manchester, UK 2 Centre for Advanced Discovery and Experimental Therapeutics (CADET), Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Sciences Centre, Manchester, UK 3 Centre for Endocrinology and Diabetes, Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, UK 4 School of Biological Sciences, University of Auckland, New Zealand 5 Department of Pharmacology, Medical Sciences Division, University of Oxford, UK † Present address: School of Biosciences, University of Birmingham, UK *Joint corresponding authors: Natalie J. Gardiner and Garth J.S. Cooper Email: [email protected]; [email protected] Address: University of Manchester, AV Hill Building, Oxford Road, Manchester, M13 9PT, United Kingdom Telephone: +44 161 275 5768; +44 161 701 0240 Word count: 4,490 Number of tables: 1, Number of figures: 6 Running title: Metabolic dysfunction in diabetic neuropathy 1 Diabetes Publish Ahead of Print, published online October 15, 2015 Diabetes Page 2 of 255 Abstract High glucose levels in the peripheral nervous system (PNS) have been implicated in the pathogenesis of diabetic neuropathy (DN). However our understanding of the molecular mechanisms which cause the marked distal pathology is incomplete. Here we performed a comprehensive, system-wide analysis of the PNS of a rodent model of DN.
    [Show full text]
  • Characterization of Nudix Hydrolases: a Utilitarian
    CHARACTERIZATION OF NUDIX HYDROLASES: A UTILITARIAN SUPERFAMILY OF ENZYMES By Andres Hernandez de la Peña A dissertation submitted to the Johns Hopkins University in conformity with the requirements for the degree of Doctor of Philosophy Baltimore, Maryland August, 2015 Abstract The present work details the structural and enzymatic characterization of Nudix hydrolases from three different organisms – Bdellovibrio bacteriovorus, Mycobacterium tuberculosis, and Tetrahymena thermophila. Each of these Nudix enzymes presents unique questions about their physiological function within their organism which are answered with a combination of structural biology, genetic manipulation, enzyme kinetics, and a wide range of protein assays. We demonstrate that RenU, from M. tuberculosis, is part of Redox Homeostasis Control System (RHOCS), which senses and regulates NADH concentrations. This control systems involves two other proteins, the serine/threonine protein kinase G (pknG) and the L13 ribosomal subunits, without which the bacterium fails to evade lysosomal delivery and falls prey to the oxidative arsenal of the macrophage host. Bd-NDPSase, a Nudix enzyme encoded by the B. bacteriovorus gene BD3179, localizes to the periplasmic space of the bacterium and hydrolyses at least four nucleoside diphosphate sugars in vitro. Through atomic-resolution models from X-ray diffraction, we identified a motif that differentiates this hydrolase from the similar, but more substrate specific, ADP- ribose hydrolase from E. coli. Lastly, we show that Nud1p from T. thermophila is a member of the Ezl1p complex, the histone methyltransferase Polycomb Group homologue of this protozoan. With the use of in vitro enzymatic assays we show, in addition, that Nu1dp hydrolyses CoA preferentially over acetyl-CoA and other nucleoside derivatives.
    [Show full text]
  • Supplemental Table 10
    Supplemental Table 10: Dietary Impact on the Heart Sulfhydrome DR/AL Accession Alternate Molecular Cysteine Spectral Protein Name Number ID Weight Residues Count Ratio P‐value Ig lambda‐2 chain C region P01844 Iglc2 11 kDa 3 C 16.000 0.00101 Gelsolin P13020 (+1) Gsn 86 kDa 7 C 11.130 0.00133 Glutamate‐‐cysteine ligase regulatory subunit O09172 Gclm 31 kDa 6 C 10.200 0.0307 Ig gamma‐3 chain C region P03987 44 kDa 10 C 7.636 0.0005 Ferritin heavy chain P09528 Fth1 21 kDa 3 C 6.182 0.02617 Antithrombin‐III P32261 Serpinc1 52 kDa 9 C 5.333 0.03116 Bisphosphoglycerate mutase P15327 Bpgm 30 kDa 3 C 4.645 0.01998 Vitamin D‐binding protein Q9QVP4 Gc 54 kDa 28 C 4.541 0.0206 Properdin P11680 Cfp 50 kDa 44 C 3.692 0.0227 Complement factor B P01867 (+1) Cfb 85 kDa 20 C 3.636 0.01126 Transforming growth factor beta‐1 P04202 Tgfb1 44 kDa 12 C 3.273 0.00601 Ferritin light chain 1 P29391 Ftl1 21 kDa 1 C 3.250 0.0204 Ig lambda‐1 chain C region Q9CPV4‐2 12 kDa 3 C 2.844 0.02618 Kininogen‐1 Q8K182 Kng1 73 kDa 19 C 2.840 0.01359 Beta‐2‐glycoprotein 1 Q01339 Apoh 39 kDa 23 C 2.691 0.00579 Complement C3 P01027 C3 186 kDa 27 C 2.556 0.00991 Complement factor I P02088 Cfi 67 kDa 40 C 2.324 0.02636 Ig heavy chain V region 102 P01750 13 kDa 3 C 16.200 0.1642 Afamin O89020 (+1) Afm 69 kDa 34 C 14.400 0.07963 Dehydrogenase/reductase SDR family member 11 Q3U0B3 Dhrs11 28 kDa 8 C 10.400 0.09207 Myosin light chain 4 P09541 Myl4 21 kDa 2 C 9.908 0.23919 Myeloperoxidase P11247 Mpo 81 kDa 16 C 8.800 0.40708 Myosin regulatory light chain 2, skeletal muscle isoform P97457
    [Show full text]
  • Association of Gene Ontology Categories with Decay Rate for Hepg2 Experiments These Tables Show Details for All Gene Ontology Categories
    Supplementary Table 1: Association of Gene Ontology Categories with Decay Rate for HepG2 Experiments These tables show details for all Gene Ontology categories. Inferences for manual classification scheme shown at the bottom. Those categories used in Figure 1A are highlighted in bold. Standard Deviations are shown in parentheses. P-values less than 1E-20 are indicated with a "0". Rate r (hour^-1) Half-life < 2hr. Decay % GO Number Category Name Probe Sets Group Non-Group Distribution p-value In-Group Non-Group Representation p-value GO:0006350 transcription 1523 0.221 (0.009) 0.127 (0.002) FASTER 0 13.1 (0.4) 4.5 (0.1) OVER 0 GO:0006351 transcription, DNA-dependent 1498 0.220 (0.009) 0.127 (0.002) FASTER 0 13.0 (0.4) 4.5 (0.1) OVER 0 GO:0006355 regulation of transcription, DNA-dependent 1163 0.230 (0.011) 0.128 (0.002) FASTER 5.00E-21 14.2 (0.5) 4.6 (0.1) OVER 0 GO:0006366 transcription from Pol II promoter 845 0.225 (0.012) 0.130 (0.002) FASTER 1.88E-14 13.0 (0.5) 4.8 (0.1) OVER 0 GO:0006139 nucleobase, nucleoside, nucleotide and nucleic acid metabolism3004 0.173 (0.006) 0.127 (0.002) FASTER 1.28E-12 8.4 (0.2) 4.5 (0.1) OVER 0 GO:0006357 regulation of transcription from Pol II promoter 487 0.231 (0.016) 0.132 (0.002) FASTER 6.05E-10 13.5 (0.6) 4.9 (0.1) OVER 0 GO:0008283 cell proliferation 625 0.189 (0.014) 0.132 (0.002) FASTER 1.95E-05 10.1 (0.6) 5.0 (0.1) OVER 1.50E-20 GO:0006513 monoubiquitination 36 0.305 (0.049) 0.134 (0.002) FASTER 2.69E-04 25.4 (4.4) 5.1 (0.1) OVER 2.04E-06 GO:0007050 cell cycle arrest 57 0.311 (0.054) 0.133 (0.002)
    [Show full text]
  • The Regulatory Roles of Phosphatases in Cancer
    Oncogene (2014) 33, 939–953 & 2014 Macmillan Publishers Limited All rights reserved 0950-9232/14 www.nature.com/onc REVIEW The regulatory roles of phosphatases in cancer J Stebbing1, LC Lit1, H Zhang, RS Darrington, O Melaiu, B Rudraraju and G Giamas The relevance of potentially reversible post-translational modifications required for controlling cellular processes in cancer is one of the most thriving arenas of cellular and molecular biology. Any alteration in the balanced equilibrium between kinases and phosphatases may result in development and progression of various diseases, including different types of cancer, though phosphatases are relatively under-studied. Loss of phosphatases such as PTEN (phosphatase and tensin homologue deleted on chromosome 10), a known tumour suppressor, across tumour types lends credence to the development of phosphatidylinositol 3--kinase inhibitors alongside the use of phosphatase expression as a biomarker, though phase 3 trial data are lacking. In this review, we give an updated report on phosphatase dysregulation linked to organ-specific malignancies. Oncogene (2014) 33, 939–953; doi:10.1038/onc.2013.80; published online 18 March 2013 Keywords: cancer; phosphatases; solid tumours GASTROINTESTINAL MALIGNANCIES abs in sera were significantly associated with poor survival in Oesophageal cancer advanced ESCC, suggesting that they may have a clinical utility in Loss of PTEN (phosphatase and tensin homologue deleted on ESCC screening and diagnosis.5 chromosome 10) expression in oesophageal cancer is frequent, Cao et al.6 investigated the role of protein tyrosine phosphatase, among other gene alterations characterizing this disease. Zhou non-receptor type 12 (PTPN12) in ESCC and showed that PTPN12 et al.1 found that overexpression of PTEN suppresses growth and protein expression is higher in normal para-cancerous tissues than induces apoptosis in oesophageal cancer cell lines, through in 20 ESCC tissues.
    [Show full text]
  • Aneuploidy: Using Genetic Instability to Preserve a Haploid Genome?
    Health Science Campus FINAL APPROVAL OF DISSERTATION Doctor of Philosophy in Biomedical Science (Cancer Biology) Aneuploidy: Using genetic instability to preserve a haploid genome? Submitted by: Ramona Ramdath In partial fulfillment of the requirements for the degree of Doctor of Philosophy in Biomedical Science Examination Committee Signature/Date Major Advisor: David Allison, M.D., Ph.D. Academic James Trempe, Ph.D. Advisory Committee: David Giovanucci, Ph.D. Randall Ruch, Ph.D. Ronald Mellgren, Ph.D. Senior Associate Dean College of Graduate Studies Michael S. Bisesi, Ph.D. Date of Defense: April 10, 2009 Aneuploidy: Using genetic instability to preserve a haploid genome? Ramona Ramdath University of Toledo, Health Science Campus 2009 Dedication I dedicate this dissertation to my grandfather who died of lung cancer two years ago, but who always instilled in us the value and importance of education. And to my mom and sister, both of whom have been pillars of support and stimulating conversations. To my sister, Rehanna, especially- I hope this inspires you to achieve all that you want to in life, academically and otherwise. ii Acknowledgements As we go through these academic journeys, there are so many along the way that make an impact not only on our work, but on our lives as well, and I would like to say a heartfelt thank you to all of those people: My Committee members- Dr. James Trempe, Dr. David Giovanucchi, Dr. Ronald Mellgren and Dr. Randall Ruch for their guidance, suggestions, support and confidence in me. My major advisor- Dr. David Allison, for his constructive criticism and positive reinforcement.
    [Show full text]
  • Supplementary Materials
    Supplementary materials Supplementary Table S1: MGNC compound library Ingredien Molecule Caco- Mol ID MW AlogP OB (%) BBB DL FASA- HL t Name Name 2 shengdi MOL012254 campesterol 400.8 7.63 37.58 1.34 0.98 0.7 0.21 20.2 shengdi MOL000519 coniferin 314.4 3.16 31.11 0.42 -0.2 0.3 0.27 74.6 beta- shengdi MOL000359 414.8 8.08 36.91 1.32 0.99 0.8 0.23 20.2 sitosterol pachymic shengdi MOL000289 528.9 6.54 33.63 0.1 -0.6 0.8 0 9.27 acid Poricoic acid shengdi MOL000291 484.7 5.64 30.52 -0.08 -0.9 0.8 0 8.67 B Chrysanthem shengdi MOL004492 585 8.24 38.72 0.51 -1 0.6 0.3 17.5 axanthin 20- shengdi MOL011455 Hexadecano 418.6 1.91 32.7 -0.24 -0.4 0.7 0.29 104 ylingenol huanglian MOL001454 berberine 336.4 3.45 36.86 1.24 0.57 0.8 0.19 6.57 huanglian MOL013352 Obacunone 454.6 2.68 43.29 0.01 -0.4 0.8 0.31 -13 huanglian MOL002894 berberrubine 322.4 3.2 35.74 1.07 0.17 0.7 0.24 6.46 huanglian MOL002897 epiberberine 336.4 3.45 43.09 1.17 0.4 0.8 0.19 6.1 huanglian MOL002903 (R)-Canadine 339.4 3.4 55.37 1.04 0.57 0.8 0.2 6.41 huanglian MOL002904 Berlambine 351.4 2.49 36.68 0.97 0.17 0.8 0.28 7.33 Corchorosid huanglian MOL002907 404.6 1.34 105 -0.91 -1.3 0.8 0.29 6.68 e A_qt Magnogrand huanglian MOL000622 266.4 1.18 63.71 0.02 -0.2 0.2 0.3 3.17 iolide huanglian MOL000762 Palmidin A 510.5 4.52 35.36 -0.38 -1.5 0.7 0.39 33.2 huanglian MOL000785 palmatine 352.4 3.65 64.6 1.33 0.37 0.7 0.13 2.25 huanglian MOL000098 quercetin 302.3 1.5 46.43 0.05 -0.8 0.3 0.38 14.4 huanglian MOL001458 coptisine 320.3 3.25 30.67 1.21 0.32 0.9 0.26 9.33 huanglian MOL002668 Worenine
    [Show full text]