Transcriptional coactivators p300 and CBP stimulate estrogen receptor‐beta signaling and regulate cellular events in prostate cancer

Abstract

p300 and CBP are implicated in regulation of ER-β activity and cellular migration in prostate cancer. These findings are important for understanding of action of ER-β in carcinoma of the prostate.

Estrogen receptor beta in prostate cancer: friend or foe?

“…It is therefore possible that PELP1 and ERB2 have a role in the promotion of prostate cancer metastasis. If correct, this hypothesis could explain the previously discussed findings of high ERB expression in bone and lymph node metastases, and the correlation between persistent ERB expression in highgrade prostate cancer and greater risk of disease relapse (Horvath et al 2001, Zhu et al 2004, Bouchal et al 2011, Zellweger et al 2013. This is an important area for further investigation.…”

“…In an additional finding that seems to contradict these results, where ERB expression was maintained, there was a higher rate of disease relapse irrespective of tumour grade (Horvath et al 2001). Other studies have demonstrated high ERB expression in bone and lymph node metastases (Zhu et al 2004, Bouchal et al 2011. A recent study has shown that the combination of ERB expression and AR phosphorylation in hormone-naïve prostate cancer correlates with poor clinical outcome (Zellweger et al 2013).…”

“…ERB2 may act as an oncogene and has been implicated specifically in the process of cancer metastasis , Leung et al 2010, Dey et al 2012. If the antibodies used in the abovementioned studies (Horvath et Printed in Great Britain Zhu et al 2004, Bouchal et al 2011, Zellweger et al 2013 are in fact detecting ERB2, rather than ERB1, some of the abovementioned contradictions may be explained. Further detailed study is required to answer this definitively.…”

“…If ERB is tumour-suppressive, then it is logical that its expression declines with advancing carcinogenesis. However, this does not explain why ERB expression is then high in lymph node or bone metastases ( Zhu et al 2004, Bouchal et al 2011, or the observed correlation between high ERB expression and poor prostate cancer prognosis (Horvath et al 2001, Zellweger et al 2013. This may be due to varying levels of promotor methylation throughout the carcinogenic process introducing reversible, stage-and tissue-specific changes in ERB expression and altering its transcriptional role , Cotrim et al 2013).…”

A phosphotyrosine switch determines the antitumor activity of ERβ

“…To elucidate the molecular basis for the role of p-Y36 in transcriptional activation, we first compared the ability of WT ERβ and Y36 mutants to bind to p300, one of the known transcriptional coactivators of ERβ (36,37). The Y36F mutant had a significantly reduced affinity for p300 as compared with WT ERβ ( Figure 4A, compare lanes 3 and 4 with 5 and 6).…”