• Login
    View Item 
    •   UMB Digital Archive
    • UMB Open Access Articles
    • UMB Open Access Articles
    • View Item
    •   UMB Digital Archive
    • UMB Open Access Articles
    • UMB Open Access Articles
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of UMB Digital ArchiveCommunitiesPublication DateAuthorsTitlesSubjectsThis CollectionPublication DateAuthorsTitlesSubjects

    My Account

    LoginRegister

    Statistics

    Display statistics

    Endogenous Retroviral-K Envelope Is a Novel Tumor Antigen and Prognostic Indicator of Renal Cell Carcinoma

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Author
    Weyerer, Veronika
    Strissel, Pamela L
    Stöhr, Christine
    Eckstein, Markus
    Wach, Sven
    Taubert, Helge
    Brandl, Lisa
    Geppert, Carol I
    Wullich, Bernd
    Cynis, Holger
    Beckmann, Matthias W
    Seliger, Barbara
    Hartmann, Arndt
    Strick, Reiner
    Show allShow less

    Date
    2021-04-22
    Journal
    Frontiers in Oncology
    Publisher
    Frontiers Media S.A.
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://doi.org/10.3389/fonc.2021.657187
    Abstract
    Renal cell carcinoma (RCC) is one of the ten most common cancers for men and women with an approximate 75% overall 5-year survival. Sixteen histological tumor subtypes exist and the most common are papillary, chromophobe and clear cell renal cell carcinoma (ccRCC) representing 85% of all RCC. Although epigenetically silenced, endogenous retroviral (ERV) genes become activated in tumors and function to ignite immune responses. Research has intensified to understand ERV protein function and their role as tumor antigens and targets for cancer (immune) therapy. ERV-K env is overexpressed and implicated as a therapeutic target for breast cancer, however studies in RCC are limited. In this investigation a human RCC tissue microarray (TMA) (n=374) predominantly consisting of the most common histological tumor subtypes was hybridized with an ERV-K env antibody and correlated with patient clinical data. TMA results showed the highest amount of ERV-K env protein expression and the strongest significant membrane expression in ccRCC versus other RCC subtypes. High ERV-K env total protein expression of all tumor subtypes significantly correlated with low tumor grading and a longer disease specific survival using multivariable analyses. Cell proliferation and invasion were assayed using the kidney cell lines HEK293 with wild-type p53 and a ccRCC cell line MZ1257RC mutated for p53. Transfecting these cell lines with a codon optimized ERV-K113 env overexpressing CMV vector was performed with or without 5'-Aza-2'-deoxycytidine (Aza) treatment to sustain promoter de-methylation. MZ1257RC showed induction of ERV-K113 expression and significantly increased both proliferation and invasion in the presence or absence of Aza. HEK293 cells demonstrated a restriction of ERV-K113 env expression and invasion with no changes in proliferation in the absence of Aza. However, in the presence of Aza despite increased ERV-K113 env expression, an inhibition of HEK293 proliferation and a further restriction of invasion was found. This study supports ERV-K env as a single prognostic indicator for better survival of RCC, which we propose represents a new tumor antigen. In addition, ERV-K env significantly regulates proliferation and invasion depending on p53 status and Aza treatment.
    Rights/Terms
    Copyright © 2021 Weyerer, Strissel, Stöhr, Eckstein, Wach, Taubert, Brandl, Geppert, Wullich, Cynis, Beckmann, Seliger, Hartmann and Strick.
    Keyword
    ERV-K
    azacytidine
    endogenous retrovirus
    invasion
    p53
    patient prognosis
    renal cell carcinoma
    tumor antigen
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/15639
    ae974a485f413a2113503eed53cd6c53
    10.3389/fonc.2021.657187
    Scopus Count
    Collections
    UMB Open Access Articles

    entitlement

    Related articles

    • Identification and validation of novel prognostic markers in Renal Cell Carcinoma.
    • Authors: Rabjerg M
    • Issue date: 2017 Oct
    • Reactivation of codogenic endogenous retroviral (ERV) envelope genes in human endometrial carcinoma and prestages: Emergence of new molecular targets.
    • Authors: Strissel PL, Ruebner M, Thiel F, Wachter D, Ekici AB, Wolf F, Thieme F, Ruprecht K, Beckmann MW, Strick R
    • Issue date: 2012 Oct
    • Metabolic and Lipidomic Reprogramming in Renal Cell Carcinoma Subtypes Reflects Regions of Tumor Origin.
    • Authors: Schaeffeler E, Büttner F, Reustle A, Klumpp V, Winter S, Rausch S, Fisel P, Hennenlotter J, Kruck S, Stenzl A, Wahrheit J, Sonntag D, Scharpf M, Fend F, Agaimy A, Hartmann A, Bedke J, Schwab M
    • Issue date: 2019 Jul
    • Identification and spontaneous immune targeting of an endogenous retrovirus K envelope protein in the Indian rhesus macaque model of human disease.
    • Authors: Wu HL, Léon EJ, Wallace LT, Nimiyongskul FA, Buechler MB, Newman LP, Castrovinci PA, Paul Johnson R, Gifford RJ, Brad Jones R, Sacha JB
    • Issue date: 2016 Jan 15
    • Tracking the Fate of Endogenous Retrovirus Segregation in Wild and Domestic Cats.
    • Authors: Ngo MH, Arnal M, Sumi R, Kawasaki J, Miyake A, Grant CK, Otoi T, Fernández de Luco D, Nishigaki K
    • Issue date: 2019 Dec 15
    DSpace software (copyright © 2002 - 2022)  DuraSpace
    Quick Guide | Policies | Contact Us | UMB Health Sciences & Human Services Library
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.