Synergism between androgens and protein kinase-C on androgen-regulated gene expression.
Androgen (R1881) induced transcriptional activity of the human androgen receptor, stably expressed in CHO cells, can be stimulated an extra 2-fold by the addition of the protein kinase C activator, 4 beta-phorbol 12-myristate 13-acetate (PMA). This extra stimulation is not observed when the protein kinase A activator bromoadenosine 3':5'-cyclic monophosphate (8-BrcAMP) is used. The transcriptional activity was measured using a reporter plasmid containing the MMTV-promoter, coupled to the luciferase gene. The effect of PMA on R1881-induced transcription was not due to a higher expression level of the androgen receptor. Also, no extra phosphorylation of the androgen receptor could be measured after incubation with PMA. When GRE-tk-LUC and PSA-LUC reporters were used, the synergistic effect of PMA could not be observed. The findings on the composite MMTV-LTR promoter can be explained by either a direct synergistic interaction between occupied AP-1 like responsive elements and the androgen receptor or via an unknown transcription factor activated by the PKC pathway and interacting with the androgen receptor.
de Ruiter
P E
PE
Department of Endocrinology and Reproduction, Erasmus University, Rotterdam, The Netherlands.
Teuwen
R
R
Trapman
J
J
Dijkema
R
R
Brinkmann
A O
AO
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D008156:Luciferases / Q000235:genetics; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics; D015741:Metribolone / Q000494:pharmacology*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D011493:Protein Kinase C / Q000378:metabolism*; D012045:Regulatory Sequences, Nucleic Acid; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic
D015741:Metribolone; D008156:Luciferases; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate