Details

Autor(en) / Beteiligte

• Wang, Qianben
• Li, Wei
• Zhang, Yong
• Yuan, Xin
• Xu, Kexin
• Yu, Jindan
• Chen, Zhong
• Beroukhim, Rameen
• Wang, Hongyun
• Lupien, Mathieu
• Wu, Tao
• Regan, Meredith M.
• Meyer, Clifford A.
• Carroll, Jason S.
• Manrai, Arjun Kumar
• Jänne, Olli A.
• Balk, Steven P.
• Mehra, Rohit
• Han, Bo
• Chinnaiyan, Arul M.
• Rubin, Mark A.
• True, Lawrence
• Fiorentino, Michelangelo
• Fiore, Christopher
• Loda, Massimo
• Kantoff, Philip W.
• Liu, X. Shirley
• Brown, Myles

Titel

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

Ist Teil von

• Cell, 2009-07, Vol.138 (2), p.245-256

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2009

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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.