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.
Wolf
D A
DA
Institut für Physiologische Chemie, Universität München, Germany.
Kohlhuber
F
F
Schulz
P
P
Fittler
F
F
Eick
D
D
D015152:Blotting, Northern; D002460:Cell Line; D002874:Chromosome Mapping; D015342:DNA Probes; D015536:Down-Regulation / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D016259:Genes, myc / Q000187:drug effects*; D006801:Humans; D008297:Male; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000503:physiopathology*; D012313:RNA / Q000096:biosynthesis
D015342:DNA Probes; D012313:RNA