TRANSCRIPTIONAL DOWN-REGULATION OF C-MYC IN HUMAN PROSTATE CARCINOMA-CELLS BY THE SYNTHETIC ANDROGEN MIBOLERONE

The mechanism of down-regulation of c-myc RNA associated with androgen-induced suppression of the transformed phenotype in the human prostate carcinoma cell line LNCaP was investigated. The synthetic androgen mibolerone (7-alpha-17-alpha-Dimethyl-19-nortestosterone) reversibly inhibits the proliferation of LNCaP cells and, from 12-72 h after hormone addition reduces the level of c-myc transcripts to a few per cent of controls. P1, P2, and P0 c-myc transcripts decline at the same rate, whereas P3 transcripts are much less hormone sensitive. Nuclear run-on analysis revealed that c-myc is down-regulated at the level of transcription initiation in LNCaP cells. The level of c-myc transcripts prevailing in untreated control cells can be restored in androgen-induced cells by excess antiandrogen, indicating the involvement of the androgen receptor in c-myc down-regulation.