SYNERGISM BETWEEN ANDROGENS AND PROTEIN-KINASE-C ON ANDROGEN-REGULATED GENE-EXPRESSION

Androgen (R1881) induced transcriptional activity of the human androge n receptor, stably expressed in CHO cells, can be stimulated an extra 2-fold by the addition of the protein kinase C activator, 4 beta-phorb ol 12-myristate 13-acetate (PMA), This extra stimulation is not observ ed when the protein kinase A activator bromoadenosine 3':5'-cyclic mon ophosphate (8-BrcAMP) is used. The transcriptional activity was measur ed using a reporter plasmid containing the MMTV-promoter, coupled to t he luciferase gene. The effect of PMA on R1881-induced transcription w as 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 finding s on the composite MMTV-LTR promoter can be explained by either a dire ct synergistic interaction between occupied AP-I like responsive eleme nts and the androgen receptor or via an unknown transcription factor a ctivated by the PKC pathway and interacting with the androgen receptor .