Viral oncogene-induced DNA damage response is activated in Kaposi sarcoma tumorigenesis

Sonja Koopal, Johanna Furuhjelm, Annika Järviluoma, Sari Jäämaa, Pawan Pyakurel, Christel Elisabeth Pussinen, Maria Wirzenius, Peter Biberfeld, Kari Alitalo, Marikki Laiho, Päivi Ojala

    Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review

    Sammanfattning

    Kaposi sarcoma is a tumor consisting of Kaposi sarcoma herpesvirus ( KSHV)-infected tumor cells that express endothelial cell (EC) markers and viral genes like v-cyclin, vFLIP, and LANA. Despite a strong link between KSHV infection and certain neoplasms, de novo virus infection of human primary cells does not readily lead to cellular transformation. We have studied the consequences of expression of v-cyclin in primary and immortalized human dermal microvascular ECs. We show that v-cyclin, which is a homolog of cellular D-type cyclins, induces replicative stress in ECs, which leads to senescence and activation of the DNA damage response. We find that antiproliferative checkpoints are activated upon KSHV infection of ECs, and in early-stage but not late-stage lesions of clinical Kaposi sarcoma specimens. These are some of the first results suggesting that DNA damage checkpoint response also functions as an anticancer barrier in virally induced cancers.
    Originalspråkengelska
    TidskriftPLoS Pathogens
    Volym3
    Utgåva9
    Sidor (från-till)1348-1360
    Antal sidor13
    DOI
    StatusPublicerad - 2007
    MoE-publikationstypA1 Tidskriftsartikel-refererad

    Citera det här

    Koopal, Sonja ; Furuhjelm, Johanna ; Järviluoma, Annika ; Jäämaa, Sari ; Pyakurel, Pawan ; Pussinen, Christel Elisabeth ; Wirzenius, Maria ; Biberfeld, Peter ; Alitalo, Kari ; Laiho, Marikki ; Ojala, Päivi. / Viral oncogene-induced DNA damage response is activated in Kaposi sarcoma tumorigenesis. I: PLoS Pathogens. 2007 ; Vol. 3, Nr. 9. s. 1348-1360.
    @article{7b32e3aaca8544e1bc815bf71848d7fb,
    title = "Viral oncogene-induced DNA damage response is activated in Kaposi sarcoma tumorigenesis",
    abstract = "Kaposi sarcoma is a tumor consisting of Kaposi sarcoma herpesvirus ( KSHV)-infected tumor cells that express endothelial cell (EC) markers and viral genes like v-cyclin, vFLIP, and LANA. Despite a strong link between KSHV infection and certain neoplasms, de novo virus infection of human primary cells does not readily lead to cellular transformation. We have studied the consequences of expression of v-cyclin in primary and immortalized human dermal microvascular ECs. We show that v-cyclin, which is a homolog of cellular D-type cyclins, induces replicative stress in ECs, which leads to senescence and activation of the DNA damage response. We find that antiproliferative checkpoints are activated upon KSHV infection of ECs, and in early-stage but not late-stage lesions of clinical Kaposi sarcoma specimens. These are some of the first results suggesting that DNA damage checkpoint response also functions as an anticancer barrier in virally induced cancers.",
    author = "Sonja Koopal and Johanna Furuhjelm and Annika J{\"a}rviluoma and Sari J{\"a}{\"a}maa and Pawan Pyakurel and Pussinen, {Christel Elisabeth} and Maria Wirzenius and Peter Biberfeld and Kari Alitalo and Marikki Laiho and P{\"a}ivi Ojala",
    year = "2007",
    doi = "10.1371/journal.ppat.0030140",
    language = "English",
    volume = "3",
    pages = "1348--1360",
    journal = "PLoS Pathogens",
    issn = "1553-7366",
    publisher = "PUBLIC LIBRARY OF SCIENCE",
    number = "9",

    }

    Viral oncogene-induced DNA damage response is activated in Kaposi sarcoma tumorigenesis. / Koopal, Sonja; Furuhjelm, Johanna; Järviluoma, Annika; Jäämaa, Sari; Pyakurel, Pawan; Pussinen, Christel Elisabeth; Wirzenius, Maria; Biberfeld, Peter; Alitalo, Kari; Laiho, Marikki; Ojala, Päivi.

    I: PLoS Pathogens, Vol. 3, Nr. 9, 2007, s. 1348-1360.

    Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review

    TY - JOUR

    T1 - Viral oncogene-induced DNA damage response is activated in Kaposi sarcoma tumorigenesis

    AU - Koopal, Sonja

    AU - Furuhjelm, Johanna

    AU - Järviluoma, Annika

    AU - Jäämaa, Sari

    AU - Pyakurel, Pawan

    AU - Pussinen, Christel Elisabeth

    AU - Wirzenius, Maria

    AU - Biberfeld, Peter

    AU - Alitalo, Kari

    AU - Laiho, Marikki

    AU - Ojala, Päivi

    PY - 2007

    Y1 - 2007

    N2 - Kaposi sarcoma is a tumor consisting of Kaposi sarcoma herpesvirus ( KSHV)-infected tumor cells that express endothelial cell (EC) markers and viral genes like v-cyclin, vFLIP, and LANA. Despite a strong link between KSHV infection and certain neoplasms, de novo virus infection of human primary cells does not readily lead to cellular transformation. We have studied the consequences of expression of v-cyclin in primary and immortalized human dermal microvascular ECs. We show that v-cyclin, which is a homolog of cellular D-type cyclins, induces replicative stress in ECs, which leads to senescence and activation of the DNA damage response. We find that antiproliferative checkpoints are activated upon KSHV infection of ECs, and in early-stage but not late-stage lesions of clinical Kaposi sarcoma specimens. These are some of the first results suggesting that DNA damage checkpoint response also functions as an anticancer barrier in virally induced cancers.

    AB - Kaposi sarcoma is a tumor consisting of Kaposi sarcoma herpesvirus ( KSHV)-infected tumor cells that express endothelial cell (EC) markers and viral genes like v-cyclin, vFLIP, and LANA. Despite a strong link between KSHV infection and certain neoplasms, de novo virus infection of human primary cells does not readily lead to cellular transformation. We have studied the consequences of expression of v-cyclin in primary and immortalized human dermal microvascular ECs. We show that v-cyclin, which is a homolog of cellular D-type cyclins, induces replicative stress in ECs, which leads to senescence and activation of the DNA damage response. We find that antiproliferative checkpoints are activated upon KSHV infection of ECs, and in early-stage but not late-stage lesions of clinical Kaposi sarcoma specimens. These are some of the first results suggesting that DNA damage checkpoint response also functions as an anticancer barrier in virally induced cancers.

    U2 - 10.1371/journal.ppat.0030140

    DO - 10.1371/journal.ppat.0030140

    M3 - Article

    VL - 3

    SP - 1348

    EP - 1360

    JO - PLoS Pathogens

    JF - PLoS Pathogens

    SN - 1553-7366

    IS - 9

    ER -