Androgen-dependent activation of human cytomegalovirus major immediate-early promoter in prostate cancer cells.
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.
Moon
Jong-Seok
JS
Department of Biochemistry and Molecular Biology, Institute of Genetic Science, Center for Chronic Metabolic Disease Research, Brain Korea 21 Project for Medical Science, Yonsei University, College of Medicine, Seodaemungu, Seoul, Korea.
Lee
Min-Young
MY
Park
Sahng Wook
SW
Han
Woong Kyu
WK
Hong
Soon-Won
SW
Ahn
Jin-Hyun
JH
Kim
Kyung-Sup
KS
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000821:virology*; D000728:Androgens / Q000494:pharmacology*; D045744:Cell Line, Tumor; D017362:Cyclic AMP Response Element-Binding Protein; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D003587:Cytomegalovirus / Q000235:genetics*; D003586:Cytomegalovirus Infections / Q000235:genetics*; D015232:Dinoprostone / Q000378:metabolism; D006801:Humans; D008297:Male; D015741:Metribolone / Q000494:pharmacology*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000821:virology*; D011493:Protein Kinase C / Q000378:metabolism; D064546:Protein Kinase C beta; D018078:Receptors, Prostaglandin E / Q000378:metabolism; D014162:Transfection
D000728:Androgens; D017362:Cyclic AMP Response Element-Binding Protein; D018078:Receptors, Prostaglandin E; D015741:Metribolone; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D015232:Dinoprostone