title: Transcriptional activity of c-Jun is critical for the suppression of AR function.
abstract: Androgen receptor (AR) signaling plays a pivotal role in growth and survival of prostate cancer cells. c-Jun is an important member of the activator protein 1 (AP-1) family and was shown to interact with AR. However, the role of c-Jun in AR signaling remains controversial, with being a coactivator or a corepressor reported. Here, utilizing multiple approaches, we show that c-Jun efficiently inhibits AR activity and the growth of prostate cancer cells. Overexpression of c-Jun inhibits not only the activities of various androgen-responsive promoters but also the transcripts of multiple AR target genes. Interestingly, long-term c-Jun overexpression also down-regulates AR expression at both the protein and mRNA levels. Molecular analysis suggests that c-Jun inhibits AR transactivation potential via an unknown target gene. The inhibition of AR by c-Jun occurs in both hormone naïve and castration-resistant prostate cancer cells. Our results unravel a novel mechanism by which c-Jun antagonizes the AR signaling.
authors.affiliation: Department of Medicinal Chemistry and Molecular Pharmacology and the Purdue University Center for Cancer Research, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Chih-Chao
authors.initials: CC
authors.lastname: Hsu
authors.forename: Chang-Deng
authors.initials: CD
authors.lastname: Hu
mesh_terms: D000818:Animals; D019556:COS Cells; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002522:Chlorocebus aethiops; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms; D016755:Proto-Oncogene Proteins c-jun / Q000502:physiology*; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014158:Transcription, Genetic; D015533:Transcriptional Activation
chemical_list: D016755:Proto-Oncogene Proteins c-jun; D011944:Receptors, Androgen