Transcriptional down-regulation of c-myc in human prostate carcinoma cells by the synthetic androgen mibolerone

Abstract

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 (7a-17a-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 analy sis 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. © Macmillan Press Ltd., 1992.