TY - GEN
T1 - The role of the transcriptional coactivator p300 in prostate cancer progression
AU - Heemers, Hannelore V.
AU - Debes, Jose D.
AU - Tindall, Donald J.
PY - 2008
Y1 - 2008
N2 - Although the factors contributing to the progression of prostate cancer (PC) remain incompletely understood, androgens have long been recognized to play a central role in this process. Upon entering PC cells, androgens bind to a cognate nuclear receptor, the androgen receptor (AR). The activated AR translocates to the nucleus, binds as a dimer to androgen response elements (AREs) in the promoter of target genes, where it recruits the coactivator proteins necessary for the formation of a productive transcriptional complex, an event crucial for PC cell viability. For many decades, the androgen dependency of PCs has been exploited therapeutically by androgen ablation strategies. Although initially successful, these forms of therapy almost inevitably fail eventually, and an androgen depletion independent (ADI) disease emerges, for which currently no cure is available. Studies from our laboratory and others demonstrate that despite low circulating levels of functional androgens, the AR is critical for the proliferation and survival of ADI PC cells. Recent data indicate that alterations in the expression and/or activity of AR coactivator proteins occur during PC progression that can foster ADI activation of the AR. Here, we have investigated the role of the coactivator p300 in AR transcriptional activity and progression of PC.
AB - Although the factors contributing to the progression of prostate cancer (PC) remain incompletely understood, androgens have long been recognized to play a central role in this process. Upon entering PC cells, androgens bind to a cognate nuclear receptor, the androgen receptor (AR). The activated AR translocates to the nucleus, binds as a dimer to androgen response elements (AREs) in the promoter of target genes, where it recruits the coactivator proteins necessary for the formation of a productive transcriptional complex, an event crucial for PC cell viability. For many decades, the androgen dependency of PCs has been exploited therapeutically by androgen ablation strategies. Although initially successful, these forms of therapy almost inevitably fail eventually, and an androgen depletion independent (ADI) disease emerges, for which currently no cure is available. Studies from our laboratory and others demonstrate that despite low circulating levels of functional androgens, the AR is critical for the proliferation and survival of ADI PC cells. Recent data indicate that alterations in the expression and/or activity of AR coactivator proteins occur during PC progression that can foster ADI activation of the AR. Here, we have investigated the role of the coactivator p300 in AR transcriptional activity and progression of PC.
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U2 - 10.1007/978-0-387-69080-3_54
DO - 10.1007/978-0-387-69080-3_54
M3 - Conference contribution
C2 - 18497079
AN - SCOPUS:46749105193
SN - 9780387690780
T3 - Advances in Experimental Medicine and Biology
SP - 535
EP - 540
BT - Hormonal Carcinogenesis V
A2 - Li, Jonathan
A2 - Li, Sara
A2 - Mohla, Suresh
A2 - Rochefort, Henri
A2 - Rochefort, Henri
A2 - Maudelonde, Thierry
ER -