Androgen-dependent activation of human cytomegalovirus major immediate-early promoter in prostate cancer cells

Abstract

BACKGROUND: Human cytomegalovirus (HCMV) major immediate early (MIE) promoter, which is involved in viral reactivation, is specifically activated by androgen in LNCaP prostate cancer cells.

METHODS: Androgen-dependent transcriptional activities of the HCMV MIE promoter were measured by transient transfection assay. Expression levels of genes related to protein kinase A (PKA)-signaling pathway was measured by RT-PCR.

RESULTS: Activation of the HCMV MIE promoter by androgen results from an increase in PKA activities. The expression level of PKA catalytic (C) subunit beta transcript variant 2 (PKA-C beta 2) was decreased by serum deprivation and was increased by R1881 treatment, in a pattern similar to changes of the HCMV MIE promoter activities. Furthermore the exogenous expression of PKA-C beta 2 strongly activated the HCMV MIE promoter, indicating that regulation of the PKA-C beta 2 expression might be a direct upstream factor in the HCMV MIE promoter regulation by androgen in LNCaP cells.

CONCLUSIONS: The data elucidated the mechanisms by which androgen activates PKA in androgen-dependent prostate cancer cells, resulting in activation of the HCMV MIE promoter. These results support the possibility that activation of the HCMV MIE promoter by androgen in the prostate could cause the productive infection, which might contribute to oncomodulation in prostate cancers.