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

    Research output: Contribution to journalArticleScientificpeer-review

    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.
    Original languageEnglish
    JournalPLoS Pathogens
    Volume3
    Issue number9
    Pages (from-to)1348-1360
    Number of pages13
    DOIs
    Publication statusPublished - 2007
    MoE publication typeA1 Journal article-refereed

    Cite this

    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. In: PLoS Pathogens. 2007 ; Vol. 3, No. 9. pp. 1348-1360.
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    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",
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    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.

    In: PLoS Pathogens, Vol. 3, No. 9, 2007, p. 1348-1360.

    Research output: Contribution to journalArticleScientificpeer-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

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    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.

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