Androgen Receptor Can Activate Different Prostate Cancer Genes

Androgen Receptor Can Activate Different Prostate Cancer Genes
In a recent study entitled “Agonist and antagonist switch DNA motifs recognized by human androgen receptor in prostate cancer”, published in the EMBO Journal, a team of researchers discovered the androgen receptors can bind to different motifs in the DNA, depending if it is an agonist (androgen hormone) or an antagonist (antiandrogen drug) of prostate cancer cells. Notably, both forms trigger transcriptional programs that induce prostate carcinogenesis. The androgen receptor is a transcription factor whose primarily function is to bind to certain DNA sequences in order to regulate gene expression. This implies that it must recognize the DNA sequence motif to bind. This receptor is activated upon binding to the hormones testosterone or dihydrotestosterone (androgen receptor agonists) but also upon binding to its antagonists, such as bicalutamide and enzalutamide. Once bound to either agonist or antagonist, it then binds DNA. However, a question that has remained unanswered is whether the same transcription factor can actually recognize and bind to different DNA motifs. With this question in mind, the research team used the androgen receptor as a model for this hypothetical differential motif-recognition theory. Researchers developed a new approach using a modified chromatin immunoprecipitation-exonuclease (ChIP-exo) technique, which allowed the identification of transcription factor binding locations, as well as its binding motifs. Using prostate cancer cell lines, malignant prostate human tumors and non-malignant adjacent tissue, the team defined the binding motifs of both agonist‐ and antagonist-bound human androgen receptor. The results showed that agonist-bound human androgen receptor (with dihydrotestosterone as the agonist) binds to the
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