Cargando…
Viral Oncogene–Induced DNA Damage Response Is Activated in Kaposi Sarcoma Tumorigenesis
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...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2007
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1994968/ https://www.ncbi.nlm.nih.gov/pubmed/17907806 http://dx.doi.org/10.1371/journal.ppat.0030140 |
_version_ | 1782135504483909632 |
---|---|
author | Koopal, Sonja Furuhjelm, Johanna H Järviluoma, Annika Jäämaa, Sari Pyakurel, Pawan Pussinen, Christel Wirzenius, Maria Biberfeld, Peter Alitalo, Kari Laiho, Marikki Ojala, Päivi M |
author_facet | Koopal, Sonja Furuhjelm, Johanna H Järviluoma, Annika Jäämaa, Sari Pyakurel, Pawan Pussinen, Christel Wirzenius, Maria Biberfeld, Peter Alitalo, Kari Laiho, Marikki Ojala, Päivi M |
author_sort | Koopal, Sonja |
collection | PubMed |
description | 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. |
format | Text |
id | pubmed-1994968 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2007 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-19949682007-09-28 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 PLoS Pathog Research Article 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. Public Library of Science 2007-09 2007-09-28 /pmc/articles/PMC1994968/ /pubmed/17907806 http://dx.doi.org/10.1371/journal.ppat.0030140 Text en © 2007 Koopal et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article 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 |
title | Viral Oncogene–Induced DNA Damage Response Is Activated in Kaposi Sarcoma Tumorigenesis |
title_full | Viral Oncogene–Induced DNA Damage Response Is Activated in Kaposi Sarcoma Tumorigenesis |
title_fullStr | Viral Oncogene–Induced DNA Damage Response Is Activated in Kaposi Sarcoma Tumorigenesis |
title_full_unstemmed | Viral Oncogene–Induced DNA Damage Response Is Activated in Kaposi Sarcoma Tumorigenesis |
title_short | Viral Oncogene–Induced DNA Damage Response Is Activated in Kaposi Sarcoma Tumorigenesis |
title_sort | viral oncogene–induced dna damage response is activated in kaposi sarcoma tumorigenesis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1994968/ https://www.ncbi.nlm.nih.gov/pubmed/17907806 http://dx.doi.org/10.1371/journal.ppat.0030140 |
work_keys_str_mv | AT koopalsonja viraloncogeneinduceddnadamageresponseisactivatedinkaposisarcomatumorigenesis AT furuhjelmjohannah viraloncogeneinduceddnadamageresponseisactivatedinkaposisarcomatumorigenesis AT jarviluomaannika viraloncogeneinduceddnadamageresponseisactivatedinkaposisarcomatumorigenesis AT jaamaasari viraloncogeneinduceddnadamageresponseisactivatedinkaposisarcomatumorigenesis AT pyakurelpawan viraloncogeneinduceddnadamageresponseisactivatedinkaposisarcomatumorigenesis AT pussinenchristel viraloncogeneinduceddnadamageresponseisactivatedinkaposisarcomatumorigenesis AT wirzeniusmaria viraloncogeneinduceddnadamageresponseisactivatedinkaposisarcomatumorigenesis AT biberfeldpeter viraloncogeneinduceddnadamageresponseisactivatedinkaposisarcomatumorigenesis AT alitalokari viraloncogeneinduceddnadamageresponseisactivatedinkaposisarcomatumorigenesis AT laihomarikki viraloncogeneinduceddnadamageresponseisactivatedinkaposisarcomatumorigenesis AT ojalapaivim viraloncogeneinduceddnadamageresponseisactivatedinkaposisarcomatumorigenesis |