| Literature DB >> 19632176 |
Qianben Wang1, Wei Li, Yong Zhang, Xin Yuan, Kexin Xu, Jindan Yu, Zhong Chen, Rameen Beroukhim, Hongyun Wang, Mathieu Lupien, Tao Wu, Meredith M Regan, Clifford A Meyer, Jason S Carroll, Arjun Kumar Manrai, Olli A Jänne, Steven P Balk, Rohit Mehra, Bo Han, Arul M Chinnaiyan, Mark A Rubin, Lawrence True, Michelangelo Fiorentino, Christopher Fiore, Massimo Loda, Philip W Kantoff, X Shirley Liu, Myles Brown.
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.Entities:
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Year: 2009 PMID： 19632176 PMCID： PMC2726827 DOI： 10.1016/j.cell.2009.04.056
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582