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

Sonja Koopal ¹, Johanna H Furuhjelm , Annika Järviluoma

⁰Genome-Scale Biology Program and Institute of Biomedicine, Biomedicum Helsinki, University of Helsinki, Finland.

Plos Pathogens +

|

October 3, 2007

View abstract on PubMed

Summary

Kaposi sarcoma herpesvirus (KSHV) v-cyclin expression causes DNA damage and senescence in endothelial cells (ECs). This DNA damage response acts as an anticancer barrier, even in KSHV-induced cancers.

Area Of Science

Oncology
Virology
Cell Biology

Background

Kaposi sarcoma (KS) is a KSHV-associated malignancy.
KSHV-infected cells express viral genes and EC markers.
De novo KSHV infection rarely transforms primary human cells.

Purpose Of The Study

Investigate the effects of v-cyclin expression in human dermal microvascular ECs.
Determine the role of v-cyclin in cellular transformation and DNA damage response.
Assess the function of antiproliferative checkpoints in KSHV-induced cancers.

Main Methods

Studied v-cyclin expression in primary and immortalized human dermal microvascular ECs.
Analyzed replicative stress, senescence, and DNA damage response activation.
Examined antiproliferative checkpoints in KSHV-infected ECs and KS lesions.

Main Results

v-cyclin, a KSHV homolog of cellular D-type cyclins, induced replicative stress in ECs.
Replicative stress led to senescence and DNA damage response activation.
Antiproliferative checkpoints were activated in KSHV-infected ECs and early-stage KS lesions.

Conclusions

v-cyclin expression triggers cellular senescence and DNA damage response in ECs.
The DNA damage checkpoint response acts as an anticancer barrier in KSHV-infected cells.
This response is functional in early-stage KS but not late-stage lesions.

Related Concept Videos