Viral Oncogene–Induced DNA Damage Response Is Activated in Kaposi Sarcoma Tumorigenesis

PLoS Pathogens

Peter Biberfeld¹  Pawan Pyakurel¹  Annika Järviluoma²  Johanna H Furuhjelm²  Christel Pussinen²  Sonja Koopal²  Päivi M Ojala²  Maria Wirzenius³  Marikki Laiho³  Kari Alitalo³  Sari Jäämaa³ 

[1] Department of Pathology and Oncology, Karolinska Institute/Hospital, Stockholm, Sweden;Genome-Scale Biology Program and Institute of Biomedicine, Biomedicum Helsinki, University of Helsinki, Finland;Molecular Cancer Biology Program, Haartman Institute, Biomedicum Helsinki, University of Helsinki, Finland

关键词: DNA damage;    Centrosomes;    Cyclins;    Carcinogenesis;    Nuclear staining;    DNA replication;    Kaposi sarcoma;    Phosphorylation;   

DOI  :  10.1371/journal.ppat.0030140

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY