Tip60 promotes prostate cancer cell proliferation by translocation of androgen receptor into the nucleus

Abstract

Tip60 is involved in the proliferation of PCa cells as an AR coactivator. Modulation of Tip60 expression or function may be a useful strategy for developing novel therapeutics for PCa, even CRPC, which remain dependent on AR signaling, by overexpressing AR and its coactivators.

Pro-survival and anti-apoptotic properties of androgen receptor signaling by oxidative stress promote treatment resistance in prostate cancer

“…Inversely, it has been reported that SOD mimetics reduce oxidative stress and exert a suppressive effect on AR expression, including the expression of AR splice variants, and have a therapeutic effect on prostate cancer cells (Thomas & Sharifi 2012 promising for the treatment of prostate cancer, including CRPC. We have also independently found that oxidative stress plays a crucial role in AR signaling, leading to the development of CRPC (Shiota et al 2010(Shiota et al , 2011a.…”

“…Oxidative stress has been shown to play an important role in the tumorigenesis and progression of prostate cancer (Bostwick et al 2000, Sharifi et al 2008, Khandrika et al 2009), as well as in the conversion of androgen-dependent prostate cancer into CRPC (Sharifi et al 2008, Shiota et al 2010, 2011a. Together, these results suggest an intimate cross-talk between oxidative stress and AR signaling.…”

“…Ripple et al (1997) reported that the physiological level of androgens decreased oxidative stress while the overloading of androgens induced oxidative stress, suggesting non-specific stress under non-physiological condition. In humans, it was found that androgen deprivation therapy decreases SOD2 expression in biopsy tissues of prostate cancer (Best et al 2005), and increases oxidative stress in prostate cancer cells as well as in surgically resected tissue of prostate cancer tissues (Shiota et al 2010(Shiota et al , 2012. In addition to androgen deprivation, several treatments against prostate cancer including taxane chemotherapy and radiotherapy are known to induce oxidative stress (Acharya et al 2010).…”

Estrogen Receptor β (ERβ1) Transactivation Is Differentially Modulated by the Transcriptional Coregulator Tip60 in a cis-Acting Element-dependent Manner

“…pGBKT7 vector containing the full-length of ER␤1, ER␣, and purified PCR product of Tip60 were, respectively, translated in vitro by the TNT T7-reticulocyte system (Promega, Fitchburg, WI) labeled with EasyTag EXPRESS 35 S protein labeling mix (PerkinElmer Life Sciences). Tip60 (10 l) and ER␤1 or ER␣ (each 10 l) proteins were mixed at 4°C for 1 h. Lysates were incubated with 20 l of EZview red anti-HA affinity gel (Sigma) at 4°C overnight with agitation.…”

“…The interaction was also confirmed in a cell line with a high endogenous level of Tip60. A prostate cancer cell line, PC-3, with ectopic expression of ER␤1 (PC-3-ER␤1) was used (35). Tip60 was coimmunoprecipitated with ER␤1 in the absence or presence of E 2 ( Fig.…”