Oncogenic Herpesvirus HHV-8 Promotes Androgen-Independent Prostate Cancer Growth

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. Cancer Res; 73(18); 5695-708. Ó2013 AACR.

Nasopharyngeal gene expression, a novel approach to study the course of respiratory syncytial virus infection

“…The downregulation of MSP was previously described in the context of rhinovirus infection [28]. MYGATT et al [29] reported virus-mediated silencing of MSP, which seems in accordance with our findings. Finally, significant upregulation of CCL7 has been observed in mice infected with rhinovirus [20] and in children during infection by different respiratory viruses, including RSV [30].…”

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