Author/Authors :
Qianben Wang، نويسنده , , Wei Li، نويسنده , , Yong Zhang، نويسنده , , Xin Yuan، نويسنده , , Fenlan Li and Kexin Xu، نويسنده , , Jindan Yu، نويسنده , , Zhong Chen، نويسنده , , Rameen Beroukhim، نويسنده , , George Oster and Hongyun Wang، نويسنده , , Mathieu Lupien، نويسنده , , Tao Wu، نويسنده , , Meredith M. Regan، نويسنده , , Clifford A. Meyer، نويسنده , , Jason S. Carroll، نويسنده , , Arjun Kumar Manrai، نويسنده , , Olli A. J?nne، نويسنده , , Steven P. Balk، نويسنده , , Rohit Mehra، نويسنده , , Bo Han، نويسنده , , Arul M. Chinnaiyan، نويسنده , , et al.، نويسنده ,
Abstract :
The evolution of prostate cancer from an androgen-dependent state to one that is androgen-independent marks its lethal progression. The androgen receptor (AR) is essential in both, though its function in androgen-independent cancers is poorly understood. We have defined the direct AR-dependent target genes in both androgen-dependent and -independent cancer cells by generating AR-dependent gene expression profiles and AR cistromes. In contrast to what is found in androgen-dependent cells, AR selectively upregulates M-phase cell-cycle genes in androgen-independent cells, including UBE2C, a gene that inactivates the M-phase checkpoint. We find that epigenetic marks at the UBE2C enhancer, notably histone H3K4 methylation and FoxA1 transcription factor binding, are present in androgen-independent cells and direct AR-enhancer binding and UBE2C activation. Thus, the role of AR in androgen-independent cancer cells is not to direct the androgen-dependent gene expression program without androgen, but rather to execute a distinct program resulting in androgen-independent growth.
