Format

Send to

Choose Destination
Cancer Res. 2013 Sep 15;73(18):5695-708. doi: 10.1158/0008-5472.CAN-12-4196. Epub 2013 Sep 4.

Oncogenic herpesvirus HHV-8 promotes androgen-independent prostate cancer growth.

Author information

1
Authors' Affiliation: Emerging Infectious Diseases Program, Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland.

Abstract

Mechanisms underlying progression to androgen-independent prostate cancer following radical ablation therapy remain poorly defined. Although intraprostatic infections have been highlighted as potential cofactors, pathogen influences on pathways that support tumor regrowth are not known. To explore this provocative concept, we derived androgen-sensitive and -insensitive prostate epithelial cells persistently infected with human herpesvirus 8 (HHV-8), an oncogenic herpesvirus that has been detected in normal prostate epithelium, prostate adenocarcinoma, and biologic fluids of patients with prostate cancer, to explore its effects on transition to hormone-refractory disease. Strikingly, we found that HHV-8 infection of androgen-sensitive prostate cancer cells conferred the capacity for androgen-independent growth. This effect was associated with altered expression and transcriptional activity of the androgen receptor (AR). However, HHV-8 infection bypassed AR signaling by promoting enhancer of zeste homolog 2 (EZH2)-mediated epigenetic silencing of tumor-suppressor genes, including MSMB and DAB2IP that are often inactivated in advanced disease. Furthermore, we found that HHV-8 triggered epithelial-to-mesenchymal transition. Although HHV-8 has not been linked etiologically to prostate cancer, virologic outcomes revealed by our study provide mechanistic insight into how intraprostatic infections could constitute risk for progression to androgen-independent metastatic disease where EZH2 has been implicated. Taken together, our findings prompt further evaluations of the relationship between HHV-8 infections and risk of advanced prostate cancer.

PMID:
24005834
DOI:
10.1158/0008-5472.CAN-12-4196
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center