DOCSLIB.ORG

Poster Session #1

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Poster Session #1 Poster Session #1 PS1-01 A negative feedback loop of vitamin D import into African American prostate cells and tissues may have implications in hormonal carcinogenesis contributing to prostate cancer disparities. J Garcia1, Z Richards2, L Nonn1 University of Illinois at Chicago1; Dana-Farber Cancer Institute, Harvard Medical School2 Introduction & Objective : Prostate cancer (PCa) is a hormonally driven cancer and is currently the third most common cancer in the US. African American (AA) men are disproportionately at risk for both PCa and vitamin D (vitD) deficiency compared to white men. The numerous chemopreventative properties of vitD and epidemiological relationship of vitD status with PCa aggressiveness and mortality has led to the hypothesis that vitD deficiency is a biological contributor to the PCa disparity in AA men. Methods : Here we examine the mechanisms that regulate hormone import into the prostate to follow-up on unexpected relationships between serum and intraprostatic vitD metabolites in AA men that our lab recently reported. Results : We also found that Megalin, a multi-liganded endocytic membrane receptor encoded by the gene LRP2, is present on prostate epithelium and is regulated by vitD. Extra-renal activity of Megalin has not been well studied as the widely accepted Free Hormone Hypothesis assumes passive diffusion of circulating free hormones into tissues. However, the presence of megalin suggests that globulin bound hormones from the circulation, including 25D bound to vitamin D binding protein (DBP) and testosterone (T) bound to sex hormone binding globulin (SHBG), are imported into prostate in a regulated manner. Moreover, we found similar relationships between serum and intraprostatic testosterone metabolites, further supporting active megalin; AA men had higher levels of dihydrotestosterone (DHT) in prostate tissue compared to white men. Examination of megalin in vitro in primary human prostate cells and in tissue explants demonstrated that globulin-bound hormones are imported into the prostate and transcriptionally active. In vitro 25D deficiency increased expression of megalin protein and LRP2 expression in cells and tissue slices. 25D decreased LRP2 promoter activity in prostate cells. We also observed megalin-mediated internalization of DBP-bound 25D and SHBG-bound T into prostate cells. Ongoing studies are examining megalin-mediated import of estrogens, which are also implicated in carcinogenesis. Conclusions : In summary our findings support the presence of a negative feedback loop in which vitD deficiency increases hormone import into prostate epithelium via Megalin. Therefore the upregulation of megalin in the setting of vitamin D deficiency may facilitate increased import of circulating sex steroids into the prostate contributing to carcinogenesis in AA men. PS1-02 Bladder Cancer Rapid Autopsy: Emerging patient-derived xenograft models for metastatic diseases H Lam1, F Vakar-Lopez, H Cheng1, M Schweizer1, P Grivas2, EY Yu1, B Montgomery1, A Hsieh3, E Corey4, J Wright University of Washington1; University of Washington/Seattle Cancer Care Alliance2; Fred Hutchinson Cancer Research Center3; University of Washington School of Medicine4 Introduction & Objective : Patients with metastatic bladder cancer have a poor prognosis with a median survival of only 9-15 months. Understanding the biology of metastatic bladder cancer has been historically difficult due to a paucity of specimens and models that recapitulate human disease. To date, xenograft models of bladder cancer have been restricted to cell line or primary bladder cancer, models reflecting metastatic disease were not available. To this end, we established a bladder cancer rapid autopsy program to systemically acquire bladder cancer metastases, and build patient-derived xenograft (PDX) and organoid models for biological studies. Methods : Patients with metastatic bladder cancer were consented and a rapid autopsy was performed 2-6 hours after death to allow acquisition of normal and metastasis specimens. Frozen and formalin-fixed and paraffin embedded specimens were deposited into our biorepository and pathological evaluation was performed on each specimen. Additionally, tumors were implanted subcutaneously into SCID mice to establish PDXs. Once PDXs were developed, PDXs were dissociated for companion organoid culture. Clinical history and treatment information was documented for each participant. Results : We have performed 12 bladder cancer rapid autopsies to date, and have acquired 110 metastatic and 55 normal specimens. The pathological subtypes of these patients include urothelial cell carcinoma (4/12), and urothelial carcinoma with squamous differentiation (4/12) and plasmacytoid variant (4/12). The cohort has been treated BCG only (1/12), chemotherapy (5/12), and chemotherapy and immune checkpoint inhibitors (6/12). The leading site of metastasis was the liver (7/12) and lung (7/12), followed by lymph node (5/12), bone (5/12), intestine (4/12), and omentum (2/12). Approximately half (5/12) of the patients had extensive liver metastases that allow acquisition of multiple tumor foci. For the first time, PDX and organoids from three metastases (liver – CoCaB 10, omentum – CoCaB 14.1, liver – CoCaB 14.2) from the same patient were successfully developed for therapeutic studies. Conclusions : This bladder cancer rapid autopsy program provides an important volume of metastatic tumor specimens for study. Importantly, the first bladder cancer PDX derived from metastasis has been developed. The availability of metastatic bladder cancer specimens, PDXs, and organoids will allow biological studies of bladder cancer metastasis, heterogeneity, and treatment resistance. PS1-03 Carcinogen-induced bladder cancer in the FVB mouse strain is associated with glandular differentiation and increased Cd274/Pdl-1 expression L Shuman1, V Osei Amponsa, J Ellis1, E Wang1, V Walter1, M Zaleski2, J Warrick, JD Raman1, D DeGraff1 Penn State College of Medicine1; Penn State Health. MS Hershey Medical Center2 Introduction & Objective : Creation of genetically engineered mouse models of bladder cancer often involves the use of several background strains in conjunction with the carcinogen N-butyl-N- (4-hydroxybutyl) nitrosamine (BBN). However, carcinogen susceptibility in commonly used strains, as well as phenotypic differences, is not well characterized. Therefore, the objective of this study is to determine differences in susceptibility and phenotypic outcome following BBN exposure of C57BL/6 and FVB mice, two strains commonly used for model development. Methods : Male C57BL/6 and FVB mice were exposed to BBN (0.05%) in drinking water for 12 and 16 weeks. Dissected bladders were characterized by histological and immunohistochemical analyses. In addition, Gene Ontology analysis was performed to identify differences in gene expression across strains following BBN exposure. Results : While the C57BL/6 strain developed non-invasive (<pT1) tumors following 12 and 16 weeks of BBN exposure, FVB mice developed muscle invasive bladder cancer with squamous and/or glandular differentiation. Interestingly, glandular differentiation was exclusively observed in the FVB strain. FVB tumors were also highly immunogenic and inflamed as indicated by high expression of Cd274 (Pdl-1), murine histocompatibility complex (H2), and pro- inflammatory cytokines (Il-5 and Il-17). Conclusions : Following BBN exposure, FVB mice undergo rapid tumorigenesis and disease progression characterized by Pdl-1 expression and development of glandular differentiation. These studies identify a degree of tumor heterogeneity in the FVB tumors previously undescribed, and identify FVB mice as a potentially useful model for the study of bladder adenocarcinoma and the inflammatory tumor microenvironment. PS1-04 Characterization of Srd5a2creErt2 Expression in the Mouse Prostate: A Potential Source of Stromal Progenitors K Wegner, J Guo, J McMahon, A McMahon, CM Vezina University of Wisconsin-Madison Introduction & Objective : Many genetic tools are available for studying prostate epithelial cells in mice, but surprisingly few have been validated for prostate stroma. The lack of genetic mouse lines targeting prostate stroma has made identification of potential stromal progenitors difficult. Pinpointing these progenitors is the first step in identifying mechanisms responsible for stromal disease causing behaviors, including proliferation, growth factor release, and extracellular matrix synthesis. Methods : This study uses the Srd5a2creErt2mouse strain which expresses cre recombinase driven by the steroid 5 alpha-reductase type 2 (Srd5a2) promoter. Six-week-old male mice received four daily 200mg/kg doses of tamoxifen to activate cre. We mapped cre expression in adult male Srd5a2creErt2 mice using a fluorescent reporter mouse strain (tdTomatofl). To examine the regenerative capacity of these cells, mice were castrated seven days after cre activation, and subcutaneous testosterone (T) capsules were implanted two weeks later. T capsules were then removed and replaced at regular intervals a total of three times. To genetically ablate SRD5A2-expressing cells, Srd5a2creErt2 mice were crossed to mice which, upon cre- mediated recombination, express diphtheria toxin A subunit (DTA). Results : Fluorescent reporter experiments reveal that Srd5a2creErt2 is highly expressed in all prostate lobes and to a lesser degree in the seminal vesicle and testis. Cells expressing cre are largely localized to the fibromuscular tunica
Load more

Recommended publications
  • Modes of Interaction of KMT2 Histone H3 Lysine 4 Methyltransferase/COMPASS Complexes with Chromatin
    cells Review Modes of Interaction of KMT2 Histone H3 Lysine 4 Methyltransferase/COMPASS Complexes with Chromatin Agnieszka Bochy ´nska,Juliane Lüscher-Firzlaff and Bernhard Lüscher * ID Institute of Biochemistry and Molecular Biology, Medical School, RWTH Aachen University, Pauwelsstrasse 30, 52057 Aachen, Germany; [email protected] (A.B.); jluescher-fi[email protected] (J.L.-F.) * Correspondence: [email protected]; Tel.: +49-241-8088850; Fax: +49-241-8082427 Received: 18 January 2018; Accepted: 27 February 2018; Published: 2 March 2018 Abstract: Regulation of gene expression is achieved by sequence-specific transcriptional regulators, which convey the information that is contained in the sequence of DNA into RNA polymerase activity. This is achieved by the recruitment of transcriptional co-factors. One of the consequences of co-factor recruitment is the control of specific properties of nucleosomes, the basic units of chromatin, and their protein components, the core histones. The main principles are to regulate the position and the characteristics of nucleosomes. The latter includes modulating the composition of core histones and their variants that are integrated into nucleosomes, and the post-translational modification of these histones referred to as histone marks. One of these marks is the methylation of lysine 4 of the core histone H3 (H3K4). While mono-methylation of H3K4 (H3K4me1) is located preferentially at active enhancers, tri-methylation (H3K4me3) is a mark found at open and potentially active promoters. Thus, H3K4 methylation is typically associated with gene transcription. The class 2 lysine methyltransferases (KMTs) are the main enzymes that methylate H3K4. KMT2 enzymes function in complexes that contain a necessary core complex composed of WDR5, RBBP5, ASH2L, and DPY30, the so-called WRAD complex.
    [Show full text]
  • 4-6 Weeks Old Female C57BL/6 Mice Obtained from Jackson Labs Were Used for Cell Isolation
    Methods Mice: 4-6 weeks old female C57BL/6 mice obtained from Jackson labs were used for cell isolation. Female Foxp3-IRES-GFP reporter mice (1), backcrossed to B6/C57 background for 10 generations, were used for the isolation of naïve CD4 and naïve CD8 cells for the RNAseq experiments. The mice were housed in pathogen-free animal facility in the La Jolla Institute for Allergy and Immunology and were used according to protocols approved by the Institutional Animal Care and use Committee. Preparation of cells: Subsets of thymocytes were isolated by cell sorting as previously described (2), after cell surface staining using CD4 (GK1.5), CD8 (53-6.7), CD3ε (145- 2C11), CD24 (M1/69) (all from Biolegend). DP cells: CD4+CD8 int/hi; CD4 SP cells: CD4CD3 hi, CD24 int/lo; CD8 SP cells: CD8 int/hi CD4 CD3 hi, CD24 int/lo (Fig S2). Peripheral subsets were isolated after pooling spleen and lymph nodes. T cells were enriched by negative isolation using Dynabeads (Dynabeads untouched mouse T cells, 11413D, Invitrogen). After surface staining for CD4 (GK1.5), CD8 (53-6.7), CD62L (MEL-14), CD25 (PC61) and CD44 (IM7), naïve CD4+CD62L hiCD25-CD44lo and naïve CD8+CD62L hiCD25-CD44lo were obtained by sorting (BD FACS Aria). Additionally, for the RNAseq experiments, CD4 and CD8 naïve cells were isolated by sorting T cells from the Foxp3- IRES-GFP mice: CD4+CD62LhiCD25–CD44lo GFP(FOXP3)– and CD8+CD62LhiCD25– CD44lo GFP(FOXP3)– (antibodies were from Biolegend). In some cases, naïve CD4 cells were cultured in vitro under Th1 or Th2 polarizing conditions (3, 4).
    [Show full text]
  • Expression Profiling of KLF4
    Expression Profiling of KLF4 AJCR0000006 Supplemental Data Figure S1. Snapshot of enriched gene sets identified by GSEA in Klf4-null MEFs. Figure S2. Snapshot of enriched gene sets identified by GSEA in wild type MEFs. 98 Am J Cancer Res 2011;1(1):85-97 Table S1: Functional Annotation Clustering of Genes Up-Regulated in Klf4 -Null MEFs ILLUMINA_ID Gene Symbol Gene Name (Description) P -value Fold-Change Cell Cycle 8.00E-03 ILMN_1217331 Mcm6 MINICHROMOSOME MAINTENANCE DEFICIENT 6 40.36 ILMN_2723931 E2f6 E2F TRANSCRIPTION FACTOR 6 26.8 ILMN_2724570 Mapk12 MITOGEN-ACTIVATED PROTEIN KINASE 12 22.19 ILMN_1218470 Cdk2 CYCLIN-DEPENDENT KINASE 2 9.32 ILMN_1234909 Tipin TIMELESS INTERACTING PROTEIN 5.3 ILMN_1212692 Mapk13 SAPK/ERK/KINASE 4 4.96 ILMN_2666690 Cul7 CULLIN 7 2.23 ILMN_2681776 Mapk6 MITOGEN ACTIVATED PROTEIN KINASE 4 2.11 ILMN_2652909 Ddit3 DNA-DAMAGE INDUCIBLE TRANSCRIPT 3 2.07 ILMN_2742152 Gadd45a GROWTH ARREST AND DNA-DAMAGE-INDUCIBLE 45 ALPHA 1.92 ILMN_1212787 Pttg1 PITUITARY TUMOR-TRANSFORMING 1 1.8 ILMN_1216721 Cdk5 CYCLIN-DEPENDENT KINASE 5 1.78 ILMN_1227009 Gas2l1 GROWTH ARREST-SPECIFIC 2 LIKE 1 1.74 ILMN_2663009 Rassf5 RAS ASSOCIATION (RALGDS/AF-6) DOMAIN FAMILY 5 1.64 ILMN_1220454 Anapc13 ANAPHASE PROMOTING COMPLEX SUBUNIT 13 1.61 ILMN_1216213 Incenp INNER CENTROMERE PROTEIN 1.56 ILMN_1256301 Rcc2 REGULATOR OF CHROMOSOME CONDENSATION 2 1.53 Extracellular Matrix 5.80E-06 ILMN_2735184 Col18a1 PROCOLLAGEN, TYPE XVIII, ALPHA 1 51.5 ILMN_1223997 Crtap CARTILAGE ASSOCIATED PROTEIN 32.74 ILMN_2753809 Mmp3 MATRIX METALLOPEPTIDASE
    [Show full text]
  • Supplemental Table S1 (A): Microarray Datasets Characteristics
    Supplemental table S1 (A): Microarray datasets characteristics Title Summary Samples Literature ref. GEO ref. Acquisition of granule Gene expression profiling of 27 (1) GSE 11859 neuron precursor identity cerebellar tumors generated and Hedgehog‐induced from various early and late medulloblastoma in mice. stage CNS progenitor cells Medulloblastomas derived Study of mouse 5 (2) GSE 7212 from Cxcr6 mutant mice medulloblastoma in response respond to treatment with to inhibitor of Smoothened a Smoothened inhibitor Expression profiles of Identification of distinct classes 10 (3) GSE 9299 mouse medulloblastoma of up‐regulated or down‐ 339 & 340 regulated genes during Hh dependent tumorigenesis Genetic alterations in Identification of differently 10 (4) GSE 6463 mouse medulloblastomas expressed genes among CGNPs 339 & and generation of tumors and CGNPs transfected with 340 from cerebellar granule retroviruses that express nmyc neuron precursors or cyclin‐d1 Patched heterozygous Analysis of granule cell 14 (5) GSE 2426 model of medulloblastoma precursors, pre‐neoplastic cells, GDS1110 and tumor cells 1. Schuller U, Heine VM, Mao J, Kho AT, Dillon AK, Han YG, et al. Acquisition of granule neuron precursor identity is a critical determinant of progenitor cell competence to form Shh‐induced medulloblastoma. Cancer Cell 2008;14:123‐134. 2. Sasai K, Romer JT, Kimura H, Eberhart DE, Rice DS, Curran T. Medulloblastomas derived from Cxcr6 mutant mice respond to treatment with a smoothened inhibitor. Cancer Res 2007;67:3871‐3877. 3. Mao J, Ligon KL, Rakhlin EY, Thayer SP, Bronson RT, Rowitch D, et al. A novel somatic mouse model to survey tumorigenic potential applied to the Hedgehog pathway. Cancer Res 2006;66:10171‐10178.
    [Show full text]
  • 1714 Gene Comprehensive Cancer Panel Enriched for Clinically Actionable Genes with Additional Biologically Relevant Genes 400-500X Average Coverage on Tumor
    xO GENE PANEL 1714 gene comprehensive cancer panel enriched for clinically actionable genes with additional biologically relevant genes 400-500x average coverage on tumor Genes A-C Genes D-F Genes G-I Genes J-L AATK ATAD2B BTG1 CDH7 CREM DACH1 EPHA1 FES G6PC3 HGF IL18RAP JADE1 LMO1 ABCA1 ATF1 BTG2 CDK1 CRHR1 DACH2 EPHA2 FEV G6PD HIF1A IL1R1 JAK1 LMO2 ABCB1 ATM BTG3 CDK10 CRK DAXX EPHA3 FGF1 GAB1 HIF1AN IL1R2 JAK2 LMO7 ABCB11 ATR BTK CDK11A CRKL DBH EPHA4 FGF10 GAB2 HIST1H1E IL1RAP JAK3 LMTK2 ABCB4 ATRX BTRC CDK11B CRLF2 DCC EPHA5 FGF11 GABPA HIST1H3B IL20RA JARID2 LMTK3 ABCC1 AURKA BUB1 CDK12 CRTC1 DCUN1D1 EPHA6 FGF12 GALNT12 HIST1H4E IL20RB JAZF1 LPHN2 ABCC2 AURKB BUB1B CDK13 CRTC2 DCUN1D2 EPHA7 FGF13 GATA1 HLA-A IL21R JMJD1C LPHN3 ABCG1 AURKC BUB3 CDK14 CRTC3 DDB2 EPHA8 FGF14 GATA2 HLA-B IL22RA1 JMJD4 LPP ABCG2 AXIN1 C11orf30 CDK15 CSF1 DDIT3 EPHB1 FGF16 GATA3 HLF IL22RA2 JMJD6 LRP1B ABI1 AXIN2 CACNA1C CDK16 CSF1R DDR1 EPHB2 FGF17 GATA5 HLTF IL23R JMJD7 LRP5 ABL1 AXL CACNA1S CDK17 CSF2RA DDR2 EPHB3 FGF18 GATA6 HMGA1 IL2RA JMJD8 LRP6 ABL2 B2M CACNB2 CDK18 CSF2RB DDX3X EPHB4 FGF19 GDNF HMGA2 IL2RB JUN LRRK2 ACE BABAM1 CADM2 CDK19 CSF3R DDX5 EPHB6 FGF2 GFI1 HMGCR IL2RG JUNB LSM1 ACSL6 BACH1 CALR CDK2 CSK DDX6 EPOR FGF20 GFI1B HNF1A IL3 JUND LTK ACTA2 BACH2 CAMTA1 CDK20 CSNK1D DEK ERBB2 FGF21 GFRA4 HNF1B IL3RA JUP LYL1 ACTC1 BAG4 CAPRIN2 CDK3 CSNK1E DHFR ERBB3 FGF22 GGCX HNRNPA3 IL4R KAT2A LYN ACVR1 BAI3 CARD10 CDK4 CTCF DHH ERBB4 FGF23 GHR HOXA10 IL5RA KAT2B LZTR1 ACVR1B BAP1 CARD11 CDK5 CTCFL DIAPH1 ERCC1 FGF3 GID4 HOXA11 IL6R KAT5 ACVR2A
    [Show full text]
  • Transcriptional and Post-Transcriptional Regulation of ATP-Binding Cassette Transporter Expression
    Transcriptional and Post-transcriptional Regulation of ATP-binding Cassette Transporter Expression by Aparna Chhibber DISSERTATION Submitted in partial satisfaction of the requirements for the degree of DOCTOR OF PHILOSOPHY in Pharmaceutical Sciences and Pbarmacogenomies in the Copyright 2014 by Aparna Chhibber ii Acknowledgements First and foremost, I would like to thank my advisor, Dr. Deanna Kroetz. More than just a research advisor, Deanna has clearly made it a priority to guide her students to become better scientists, and I am grateful for the countless hours she has spent editing papers, developing presentations, discussing research, and so much more. I would not have made it this far without her support and guidance. My thesis committee has provided valuable advice through the years. Dr. Nadav Ahituv in particular has been a source of support from my first year in the graduate program as my academic advisor, qualifying exam committee chair, and finally thesis committee member. Dr. Kathy Giacomini graciously stepped in as a member of my thesis committee in my 3rd year, and Dr. Steven Brenner provided valuable input as thesis committee member in my 2nd year. My labmates over the past five years have been incredible colleagues and friends. Dr. Svetlana Markova first welcomed me into the lab and taught me numerous laboratory techniques, and has always been willing to act as a sounding board. Michael Martin has been my partner-in-crime in the lab from the beginning, and has made my days in lab fly by. Dr. Yingmei Lui has made the lab run smoothly, and has always been willing to jump in to help me at a moment’s notice.
    [Show full text]
  • Cpg Islands and the Regulation of Transcription
    Downloaded from genesdev.cshlp.org on September 24, 2021 - Published by Cold Spring Harbor Laboratory Press REVIEW CpG islands and the regulation of transcription Aime´e M. Deaton and Adrian Bird1 The Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh EH9 3JR, United Kingdom Vertebrate CpG islands (CGIs) are short interspersed DNA In spite of their link with transcription, the functional sequences that deviate significantly from the average significance of CGIs is only just beginning to emerge. CGI genomic pattern by being GC-rich, CpG-rich, and pre- promoters turn out to have distinctive patterns of tran- dominantly nonmethylated. Most, perhaps all, CGIs are scription initiation and chromatin configuration. Their sites of transcription initiation, including thousands that regulation involves proteins (some of which specifically are remote from currently annotated promoters. Shared bind nonmethylated CpG) that influence the modifica- DNA sequence features adapt CGIs for promoter function tion status of CGI chromatin. In addition, the CpG moieties by destabilizing nucleosomes and attracting proteins that themselves are sometimes subject to cytosine methylation, create a transcriptionally permissive chromatin state. which correlates with stable shutdown of the associated Silencing of CGI promoters is achieved through dense promoter. Here we examine the properties shared by ver- CpG methylation or polycomb recruitment, again using tebrate CGIs and how transcription is regulated at these their distinctive DNA sequence composition. CGIs are sites. Recent related reviews include Illingworth and Bird therefore generically equipped to influence local chroma- (2009), Mohn and Schubeler (2009), and Blackledge and tin structure and simplify regulation of gene activity. Klose (2011). Vertebrate genomes are methylated predominantly at the Evolutionary conservation of CGIs dinucleotide CpG, and consequently are CpG-deficient owing to the mutagenic properties of methylcytosine CGIs are distinct in vertebrates due to their lack of DNA (Coulondre et al.
    [Show full text]
  • Human Induced Pluripotent Stem Cell–Derived Podocytes Mature Into Vascularized Glomeruli Upon Experimental Transplantation
    BASIC RESEARCH www.jasn.org Human Induced Pluripotent Stem Cell–Derived Podocytes Mature into Vascularized Glomeruli upon Experimental Transplantation † Sazia Sharmin,* Atsuhiro Taguchi,* Yusuke Kaku,* Yasuhiro Yoshimura,* Tomoko Ohmori,* ‡ † ‡ Tetsushi Sakuma, Masashi Mukoyama, Takashi Yamamoto, Hidetake Kurihara,§ and | Ryuichi Nishinakamura* *Department of Kidney Development, Institute of Molecular Embryology and Genetics, and †Department of Nephrology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan; ‡Department of Mathematical and Life Sciences, Graduate School of Science, Hiroshima University, Hiroshima, Japan; §Division of Anatomy, Juntendo University School of Medicine, Tokyo, Japan; and |Japan Science and Technology Agency, CREST, Kumamoto, Japan ABSTRACT Glomerular podocytes express proteins, such as nephrin, that constitute the slit diaphragm, thereby contributing to the filtration process in the kidney. Glomerular development has been analyzed mainly in mice, whereas analysis of human kidney development has been minimal because of limited access to embryonic kidneys. We previously reported the induction of three-dimensional primordial glomeruli from human induced pluripotent stem (iPS) cells. Here, using transcription activator–like effector nuclease-mediated homologous recombination, we generated human iPS cell lines that express green fluorescent protein (GFP) in the NPHS1 locus, which encodes nephrin, and we show that GFP expression facilitated accurate visualization of nephrin-positive podocyte formation in
    [Show full text]
  • Trim24-Regulated Estrogen Response Is Dependent on Specific Histone Modifications in Breast Cancer Cells
    The Texas Medical Center Library DigitalCommons@TMC The University of Texas MD Anderson Cancer Center UTHealth Graduate School of The University of Texas MD Anderson Cancer Biomedical Sciences Dissertations and Theses Center UTHealth Graduate School of (Open Access) Biomedical Sciences 12-2012 TRIM24-REGULATED ESTROGEN RESPONSE IS DEPENDENT ON SPECIFIC HISTONE MODIFICATIONS IN BREAST CANCER CELLS Teresa T. Yiu Follow this and additional works at: https://digitalcommons.library.tmc.edu/utgsbs_dissertations Part of the Biochemistry Commons, Cancer Biology Commons, Medicine and Health Sciences Commons, and the Molecular Biology Commons Recommended Citation Yiu, Teresa T., "TRIM24-REGULATED ESTROGEN RESPONSE IS DEPENDENT ON SPECIFIC HISTONE MODIFICATIONS IN BREAST CANCER CELLS" (2012). The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access). 313. https://digitalcommons.library.tmc.edu/utgsbs_dissertations/313 This Dissertation (PhD) is brought to you for free and open access by the The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences at DigitalCommons@TMC. It has been accepted for inclusion in The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access) by an authorized administrator of DigitalCommons@TMC. For more information, please contact [email protected]. TRIM24-REGULATED ESTROGEN RESPONSE IS DEPENDENT ON SPECIFIC HISTONE
    [Show full text]
  • Inhibitor of Growth 4 (ING4) Is a Positive Regulator of Rrna Synthesis
    www.nature.com/scientificreports OPEN Inhibitor of Growth 4 (ING4) is a positive regulator of rRNA synthesis Duc-Anh Trinh 1,2, Ryutaro Shirakawa2, Tomohiro Kimura2,3, Natsumi Sakata2, Kota Goto2 & Hisanori Horiuchi1,2* Ribosome biogenesis is essential for maintaining basic cellular activities although its mechanism is not fully understood. Inhibitor of growth 4 (ING4) is a member of ING family while its cellular functions remain controversial. Here, we identifed several nucleolar proteins as novel ING4 interacting proteins. ING4 localized in the nucleus with strong accumulation in the nucleolus through its plant homeodomain, which is known to interact with histone trimethylated H3K4, commonly present in the promoter of active genes. ING4 defcient cells exhibited slower proliferation and the alteration in nucleolar structure with reduced rRNA transcription, which was rescued by exogenous expression of GFP-ING4 to the similar levels of wild type cells. In the ING4 defcient cells, histone H3K9 acetylation and the key rRNA transcription factor UBF at the promoter of rDNA were reduced, both of which were also recovered by exogenous GFP-ING4 expression. Thus, ING4 could positively regulate rRNA transcription through modulation of histone modifcations at the rDNA promoter. Inhibitor of Growth (ING) protein family is composed of 5 members, which share a highly conserved homol- ogous plant-homeodomain (PHD) at their C-terminus. PHD domain has emerged as a binding domain of tri- methylated histone H3 lysine 4 (H3K4me3)1, commonly present in the promoter region of an active gene2. ING1, the prototype member of ING family, has frst been demonstrated to inhibit cell proliferation3. Considering their structural similarity, all ING members had been proposed to be common in inhibition of cell growth and func- tion as tumor suppressors4,5.
    [Show full text]
  • The Kinesin Spindle Protein Inhibitor Filanesib Enhances the Activity of Pomalidomide and Dexamethasone in Multiple Myeloma
    Plasma Cell Disorders SUPPLEMENTARY APPENDIX The kinesin spindle protein inhibitor filanesib enhances the activity of pomalidomide and dexamethasone in multiple myeloma Susana Hernández-García, 1 Laura San-Segundo, 1 Lorena González-Méndez, 1 Luis A. Corchete, 1 Irena Misiewicz- Krzeminska, 1,2 Montserrat Martín-Sánchez, 1 Ana-Alicia López-Iglesias, 1 Esperanza Macarena Algarín, 1 Pedro Mogollón, 1 Andrea Díaz-Tejedor, 1 Teresa Paíno, 1 Brian Tunquist, 3 María-Victoria Mateos, 1 Norma C Gutiérrez, 1 Elena Díaz- Rodriguez, 1 Mercedes Garayoa 1* and Enrique M Ocio 1* 1Centro Investigación del Cáncer-IBMCC (CSIC-USAL) and Hospital Universitario-IBSAL, Salamanca, Spain; 2National Medicines Insti - tute, Warsaw, Poland and 3Array BioPharma, Boulder, Colorado, USA *MG and EMO contributed equally to this work ©2017 Ferrata Storti Foundation. This is an open-access paper. doi:10.3324/haematol. 2017.168666 Received: March 13, 2017. Accepted: August 29, 2017. Pre-published: August 31, 2017. Correspondence: [email protected] MATERIAL AND METHODS Reagents and drugs. Filanesib (F) was provided by Array BioPharma Inc. (Boulder, CO, USA). Thalidomide (T), lenalidomide (L) and pomalidomide (P) were purchased from Selleckchem (Houston, TX, USA), dexamethasone (D) from Sigma-Aldrich (St Louis, MO, USA) and bortezomib from LC Laboratories (Woburn, MA, USA). Generic chemicals were acquired from Sigma Chemical Co., Roche Biochemicals (Mannheim, Germany), Merck & Co., Inc. (Darmstadt, Germany). MM cell lines, patient samples and cultures. Origin, authentication and in vitro growth conditions of human MM cell lines have already been characterized (17, 18). The study of drug activity in the presence of IL-6, IGF-1 or in co-culture with primary bone marrow mesenchymal stromal cells (BMSCs) or the human mesenchymal stromal cell line (hMSC–TERT) was performed as described previously (19, 20).
    [Show full text]
  • Xo PANEL DNA GENE LIST
    xO PANEL DNA GENE LIST ~1700 gene comprehensive cancer panel enriched for clinically actionable genes with additional biologically relevant genes (at 400 -500x average coverage on tumor) Genes A-C Genes D-F Genes G-I Genes J-L AATK ATAD2B BTG1 CDH7 CREM DACH1 EPHA1 FES G6PC3 HGF IL18RAP JADE1 LMO1 ABCA1 ATF1 BTG2 CDK1 CRHR1 DACH2 EPHA2 FEV G6PD HIF1A IL1R1 JAK1 LMO2 ABCB1 ATM BTG3 CDK10 CRK DAXX EPHA3 FGF1 GAB1 HIF1AN IL1R2 JAK2 LMO7 ABCB11 ATR BTK CDK11A CRKL DBH EPHA4 FGF10 GAB2 HIST1H1E IL1RAP JAK3 LMTK2 ABCB4 ATRX BTRC CDK11B CRLF2 DCC EPHA5 FGF11 GABPA HIST1H3B IL20RA JARID2 LMTK3 ABCC1 AURKA BUB1 CDK12 CRTC1 DCUN1D1 EPHA6 FGF12 GALNT12 HIST1H4E IL20RB JAZF1 LPHN2 ABCC2 AURKB BUB1B CDK13 CRTC2 DCUN1D2 EPHA7 FGF13 GATA1 HLA-A IL21R JMJD1C LPHN3 ABCG1 AURKC BUB3 CDK14 CRTC3 DDB2 EPHA8 FGF14 GATA2 HLA-B IL22RA1 JMJD4 LPP ABCG2 AXIN1 C11orf30 CDK15 CSF1 DDIT3 EPHB1 FGF16 GATA3 HLF IL22RA2 JMJD6 LRP1B ABI1 AXIN2 CACNA1C CDK16 CSF1R DDR1 EPHB2 FGF17 GATA5 HLTF IL23R JMJD7 LRP5 ABL1 AXL CACNA1S CDK17 CSF2RA DDR2 EPHB3 FGF18 GATA6 HMGA1 IL2RA JMJD8 LRP6 ABL2 B2M CACNB2 CDK18 CSF2RB DDX3X EPHB4 FGF19 GDNF HMGA2 IL2RB JUN LRRK2 ACE BABAM1 CADM2 CDK19 CSF3R DDX5 EPHB6 FGF2 GFI1 HMGCR IL2RG JUNB LSM1 ACSL6 BACH1 CALR CDK2 CSK DDX6 EPOR FGF20 GFI1B HNF1A IL3 JUND LTK ACTA2 BACH2 CAMTA1 CDK20 CSNK1D DEK ERBB2 FGF21 GFRA4 HNF1B IL3RA JUP LYL1 ACTC1 BAG4 CAPRIN2 CDK3 CSNK1E DHFR ERBB3 FGF22 GGCX HNRNPA3 IL4R KAT2A LYN ACVR1 BAI3 CARD10 CDK4 CTCF DHH ERBB4 FGF23 GHR HOXA10 IL5RA KAT2B LZTR1 ACVR1B BAP1 CARD11 CDK5 CTCFL DIAPH1 ERCC1 FGF3 GID4 HOXA11
    [Show full text]