Elucidating the role of androgen receptor in breast cancer
MYC is one of the most frequently activated oncogenes in a wide variety of human cancers with a broad influence on cell proliferation, survival, differentiation, and genetic stability. However, the role of MYC and MYC target genes in androgen-controlled breast cancer growth remains unclear.
Recent genome-wide identification of MYC-binding sites and target genes greatly advanced our understanding of the complex nature of MYC action on gene regulation in tumorigenesis and stem cell differentiation (Li et al. Here, we report a novel regulatory network in molecular apocrine breast cancers regulated by AR and MYC.
In eukaryotic genomes, nuclear receptors interact with coregulators in cooperation with chromatin remodeling factors to control complex regulation of hormone-stimulated gene transcription. Pioneer factors have the capacity to interact with condensed chromatin and facilitate chromatin opening, which enables competence for recruitment of other regulatory complexes.We therefore tested whether TCF7L2 and FOXA1 proteins physically interact in MDA-MB-453 cells. 1A) suggests that TCF7L2, FOXA1, and AR may cooperate in regulating an androgen-dependent transcriptional network.Of note, we observed that the level of AR coimmunoprecipitated with TCF7L2 or FOXA1 increased upon DHT stimulation (Fig.Androgen-stimulated growth of the molecular apocrine breast cancer subtype is mediated by an androgen receptor (AR)-regulated transcriptional program.However, the molecular details of this AR-centered regulatory network and the roles of other transcription factors that cooperate with AR in the network remain elusive.