Androgen Receptor Regulates a Distinct Transcription Program in Androgen-Independent Prostate Cancer

By Qianben Wang, Yong Zhang, Xin Yuan, Kexin Xu, Jindan Yu, Zhong Chen, Rameen Beroukhim, Hongyun Wang, M. Lupien, Tao Wu and 17 more. Cell, 2009

934 citations recorded by the source corpus.

SUMMARY The evolution of prostate cancer from an androgen-dependent state (ADPCa) to one that is androgen-independent (AIPCa) marks its lethal progression. The androgen receptor (AR) is essential in both, though its function in AIPCa is poorly understood. We have defined the direct AR-dependent target genes in both AIPCa and ADPCa by generating AR-dependent gene expression profiles and AR cistromes. In contrast to ADPCa, AR selectively up-regulates M-phase cell cycle genes in AIPCa including UBE2C, a gene that inactivates the M-phase checkpoint. Selective epigenetic marks and collaborating transcription factor occupancy at UBE2C enhancers leads to increased AR recruitment and UBE2C over-expression in AIPCa cell lines and clinical cases. Silencing of UBE2C blocks AIPCa but not ADPCa growth. Thus the role of AR in AIPCa is not to direct the androgen-dependent gene expression program without androgen, but rather to execute a distinct program resulting in androgen-independent growth.

Subfields: Cancer Research, Genetics, Pulmonary and Respiratory Medicine

View Paper: https://www.semanticscholar.org/paper/935812aaf5283ec7b4d7662bc976d64ac2e0e735

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cancer Research

1. Arul M. Chinnaiyan
2. Rory Stark

In Genetics

1. Jason S. Carroll
2. Zhaohui S. Qin
3. Arul M. Chinnaiyan
4. K. Zaret
5. Rory Stark

In Pulmonary and Respiratory Medicine

1. Arul M. Chinnaiyan

Citations in the corpus

• Dual role of FoxA1 in androgen receptor binding to chromatin, androgen signalling and prostate cancer (2011, background): “This receptor also plays an important role in both androgen-dependent and castration-resistant prostate cancer (Wang et al, 2009).”
• Molecular genetics of prostate cancer: new prospects for old challenges. (2010, background): “Furthermore, recent studies have identified a rare luminal population of CARNs in the regressed prostate epithelium that displays stem cell properties during prostate regeneration (X Wang et al. 2009).”
• Pioneer transcription factors: establishing competence for gene expression. (2011, background): “Silencing of FoxA1 decreases AR binding (Wang et al. 2009) but simultaneously induces numerous new AR-binding events (D Wang et al.”
• The androgen receptor fuels prostate cancer by regulating central metabolism and biosynthesis (2011, methodology): “…important insights into the mechanisms which direct AR signalling (e.g., FOXA1 as an AR pioneer factor) and have identified castrate-resistant disease-specific AR signalling changes (e.g., UBE2C as an AR target only in castrate-resistant prostate cancer) (Wang et al, 2007, 2009; Jia et al, 2008).”
• An Integrated Network of Androgen Receptor, Polycomb, and TMPRSS2-ERG Gene Fusions in Prostate Cancer Progression (2010, background): “In LNCaP cells our study revealed 37,193 AR binding peaks, which include 82% of the AR-bound sites previously reported by ChIP-on-chip assay (Wang et al., 2009).”