Project description:The Androgen Receptor plays in general an important role in Prostate Cancer biology. The Androgen Receptor orchestrates as transcription factor the activity of AR-regulated genes at destinct genomic regions by binding to specific sequences (known as Androgen Responsive Elements - ARE). However, the biophysical nature of the Androgen Receptor at these binding sites on the DNA are not well characterized. In order to investigate the biophysical properties of these molecules at AR binding sites by super resolution microscopy in living cells, we performed a AR-ChIP sequencing for the PC346C target cell line. Based on the sequencing results, we selected certain target regions based on relative AR-enrichment for further studying the local AR dynamics in these target regions.
Project description:Androgen receptor (AR) and hypoxia inducible factor 1a (HIF1a) are transcription factors that promote prostate cancer progression. This study investigated the relationship between the AR and HIF1a signaling pathways. ChIP-seq analysis was performed on the LNCaP cell line to identify global HIF and AR binding sites within the genome, under hypoxia and normoxia and in the presence and absence of androgen treatment.
Project description:Breast cancer is a heterogeneous disease and several distinct subtypes exist based on differential gene expression patterns. Molecular apocrine tumours were recently identified as an additional subgroup, characterised as oestrogen receptor negative and androgen receptor positive (ER_ AR+), but with an expression profile resembling ER+ luminal breast cancer. One possible explanation for the apparent incongruity is that ER gene expression programmes could be recapitulated by AR. Using a cell line model of ER_ AR+ molecular apocrine tumours (termed MDA-MB-453 cells), we map global AR binding events and find a binding profile that is similar to ER binding in breast cancer cells. We find that AR binding is a near-perfect subset of FoxA1 binding regions, a level of concordance never previously seen with a nuclear receptor. AR functionality is dependent on FoxA1, since silencing of FoxA1 inhibits AR binding, expression of the majority of the molecular apocrine gene signature and growth cell growth. These findings show that AR binds and regulates ER cis-regulatory elements in molecular apocrine tumours, resulting in a transcriptional programme reminiscent of ER-mediated transcription in luminal breast cancers.
Project description:We performed androgen receptor (AR) ChIP-seq after GFP control or FOXA1 over-expression in two AR driven cancer models; LNCaP prostate cancer cell line and MDA-MB-453 molecular apocrine breast cancer cell line.
Project description:We report that p53 knockdown changed AR-DNA binding across the genome. We found fewer AR-binding sites in the absence of p53. Examination of AR-DNA binding after p53 knockdown in LNCaP cells