Abstract
In this study we report that deletion of E6-associated protein (E6-AP) in mice results in a smaller prostate gland compared with that in normal wildtype animals. To investigate the mechanism(s) by which E6-AP affects prostate gland growth and development, we carried out both in vitro and in vivo experiments. In this study we show that E6-AP interacts with androgen receptor (AR) in a hormone-dependent manner and enhances the transactivation function of AR. Our in vivo data from E6-AP-null prostate glands show that the level of AR protein is elevated while the level of the AR target protein, probasin, is decreased. In contrast, the level of AR protein is decreased, and its target protein is increased in an E6-AP-overexpressing stable cell line, suggesting that E6-AP modulates both the protein level and the activity of AR. In addition, we show that the levels of phosphatidylinositol 3-kinase, total Akt, and phosphorylated Akt are decreased in E6-AP-null prostate, suggesting that E6-AP deletion down-regulates the signaling of the phosphatidylinositol 3-kinase-Akt pathway. We also show that RhoA negatively regulates AR function, and RhoA levels are increased in E6-AP-null prostate. Furthermore, expression levels of p53, Bax, active caspases, and apoptotic index are increased in E6-AP-null prostate. Collectively, our data suggest that E6-AP deletion attenuates the growth and development of the prostate gland by interfering with AR function as well as by stimulating p53-mediated apoptosis.
| Original language | English |
|---|---|
| Pages (from-to) | 544-559 |
| Number of pages | 16 |
| Journal | Molecular Endocrinology |
| Volume | 20 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 2006 |
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All Science Journal Classification (ASJC) codes
- Molecular Biology
- Endocrinology, Diabetes and Metabolism
Cite this
Multifunction steroid receptor coactivator, E6-associated protein, is involved in development of the prostate gland. / Khan, Obaid Y.; Fu, Guilian; Ismail, Ayesha; Srinivasan, Sathish; Cao, Xuni; Tu, Yaping; Lu, Shan; Nawaz, Zafar.
In: Molecular Endocrinology, Vol. 20, No. 3, 03.2006, p. 544-559.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Multifunction steroid receptor coactivator, E6-associated protein, is involved in development of the prostate gland
AU - Khan, Obaid Y.
AU - Fu, Guilian
AU - Ismail, Ayesha
AU - Srinivasan, Sathish
AU - Cao, Xuni
AU - Tu, Yaping
AU - Lu, Shan
AU - Nawaz, Zafar
PY - 2006/3
Y1 - 2006/3
N2 - In this study we report that deletion of E6-associated protein (E6-AP) in mice results in a smaller prostate gland compared with that in normal wildtype animals. To investigate the mechanism(s) by which E6-AP affects prostate gland growth and development, we carried out both in vitro and in vivo experiments. In this study we show that E6-AP interacts with androgen receptor (AR) in a hormone-dependent manner and enhances the transactivation function of AR. Our in vivo data from E6-AP-null prostate glands show that the level of AR protein is elevated while the level of the AR target protein, probasin, is decreased. In contrast, the level of AR protein is decreased, and its target protein is increased in an E6-AP-overexpressing stable cell line, suggesting that E6-AP modulates both the protein level and the activity of AR. In addition, we show that the levels of phosphatidylinositol 3-kinase, total Akt, and phosphorylated Akt are decreased in E6-AP-null prostate, suggesting that E6-AP deletion down-regulates the signaling of the phosphatidylinositol 3-kinase-Akt pathway. We also show that RhoA negatively regulates AR function, and RhoA levels are increased in E6-AP-null prostate. Furthermore, expression levels of p53, Bax, active caspases, and apoptotic index are increased in E6-AP-null prostate. Collectively, our data suggest that E6-AP deletion attenuates the growth and development of the prostate gland by interfering with AR function as well as by stimulating p53-mediated apoptosis.
AB - In this study we report that deletion of E6-associated protein (E6-AP) in mice results in a smaller prostate gland compared with that in normal wildtype animals. To investigate the mechanism(s) by which E6-AP affects prostate gland growth and development, we carried out both in vitro and in vivo experiments. In this study we show that E6-AP interacts with androgen receptor (AR) in a hormone-dependent manner and enhances the transactivation function of AR. Our in vivo data from E6-AP-null prostate glands show that the level of AR protein is elevated while the level of the AR target protein, probasin, is decreased. In contrast, the level of AR protein is decreased, and its target protein is increased in an E6-AP-overexpressing stable cell line, suggesting that E6-AP modulates both the protein level and the activity of AR. In addition, we show that the levels of phosphatidylinositol 3-kinase, total Akt, and phosphorylated Akt are decreased in E6-AP-null prostate, suggesting that E6-AP deletion down-regulates the signaling of the phosphatidylinositol 3-kinase-Akt pathway. We also show that RhoA negatively regulates AR function, and RhoA levels are increased in E6-AP-null prostate. Furthermore, expression levels of p53, Bax, active caspases, and apoptotic index are increased in E6-AP-null prostate. Collectively, our data suggest that E6-AP deletion attenuates the growth and development of the prostate gland by interfering with AR function as well as by stimulating p53-mediated apoptosis.
UR - http://www.scopus.com/inward/record.url?scp=33344469819&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33344469819&partnerID=8YFLogxK
U2 - 10.1210/me.2005-0110
DO - 10.1210/me.2005-0110
M3 - Article
C2 - 16254014
AN - SCOPUS:33344469819
VL - 20
SP - 544
EP - 559
JO - Molecular Endocrinology
JF - Molecular Endocrinology
SN - 0888-8809
IS - 3
ER -