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

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

Research output: Contribution to journalArticle

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 (US)
Pages (from-to)1348-1360
Number of pages13
JournalPLoS Pathogens
Volume3
Issue number9
DOIs
StatePublished - Sep 2007
Externally publishedYes

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Kaposi's Sarcoma
Oncogenes
DNA Damage
Carcinogenesis
Cyclins
Herpesviridae Infections
Neoplasms
Cyclin D
Viral Genes
Herpesviridae
Virus Diseases
Endothelial Cells
Skin

ASJC Scopus subject areas

  • Microbiology
  • Parasitology
  • Virology
  • Immunology
  • Genetics
  • Molecular Biology

Cite this

Koopal, S., Furuhjelm, J. H., Järviluoma, A., Jäämaa, S., Pyakurel, P., Pussinen, C., ... Ojala, P. M. (2007). Viral oncogene-induced DNA damage response is activated in Kaposi sarcoma tumorigenesis. PLoS Pathogens, 3(9), 1348-1360. https://doi.org/10.1371/journal.ppat.0030140

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

In: PLoS Pathogens, Vol. 3, No. 9, 09.2007, p. 1348-1360.

Research output: Contribution to journalArticle

Koopal, S, Furuhjelm, JH, Järviluoma, A, Jäämaa, S, Pyakurel, P, Pussinen, C, Wirzenius, M, Biberfeld, P, Alitalo, K, Laiho, M & Ojala, PM 2007, 'Viral oncogene-induced DNA damage response is activated in Kaposi sarcoma tumorigenesis', PLoS Pathogens, vol. 3, no. 9, pp. 1348-1360. https://doi.org/10.1371/journal.ppat.0030140
Koopal S, Furuhjelm JH, Järviluoma A, Jäämaa S, Pyakurel P, Pussinen C et al. Viral oncogene-induced DNA damage response is activated in Kaposi sarcoma tumorigenesis. PLoS Pathogens. 2007 Sep;3(9):1348-1360. https://doi.org/10.1371/journal.ppat.0030140
Koopal, Sonja ; Furuhjelm, Johanna H. ; Järviluoma, Annika ; Jäämaa, Sari ; Pyakurel, Pawan ; Pussinen, Christel ; Wirzenius, Maria ; Biberfeld, Peter ; Alitalo, Kari ; Laiho, Marikki ; Ojala, Päivi M. / 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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