Back to Search
Start Over
Interleukin-4 enhances prostate-specific antigen expression by activation of the androgen receptor and Akt pathway.
- Source :
-
Oncogene . 9/11/2003, Vol. 22 Issue 39, p6037-6044. 8p. 4 Diagrams, 4 Graphs. - Publication Year :
- 2003
-
Abstract
- Androgen receptor (AR) plays an important role in the development and progression of prostate cancer upon the action of androgen through the binding of the androgen-responsive elements (AREs) on the target genes. Abnormal activation of the AR by nonandrogen has been implicated in the progression of androgen-independent prostate cancer. The levels of interleukin-4 (IL-4) are significantly elevated in sera of patients with hormone refractory prostate cancer. The potential role of IL-4 on the activation of AR was investigated in prostate cancer cells. IL-4 enhances AR-mediated prostate-specific antigen (PSA) expression and ARE-containing gene activity through activation of the AR in the androgen ablation condition in human prostate cancer cells. The AR can also be sensitized by IL-4 and activated by significantly lower levels of androgen (10?pM of R1881) in prostate cancer cells. IL-4 enhances nuclear translocation of AR and increases binding of the AR to the ARE in LNCaP prostate cancer cells. Blocking of the Akt pathway by an Akt-specific inhibitor LY294002 abrogates IL-4-induced PSA expression and AR signaling. These results demonstrate that IL-4 enhances PSA expression through activation of the AR and Akt signaling pathways in LNCaP prostate cancer cells. Understanding IL-4-induced signaling leading to abnormal activation of AR will provide insights into the molecular mechanisms of androgen-independent progression of prostate cancer cells.Oncogene (2003) 22, 6037-6044. doi:10.1038/sj.onc.1206735 [ABSTRACT FROM AUTHOR]
- Subjects :
- *ANDROGENS
*TRANS men
*PROSTATE cancer
*GENES
*INTERLEUKIN-4
*CANCER cells
Subjects
Details
- Language :
- English
- ISSN :
- 09509232
- Volume :
- 22
- Issue :
- 39
- Database :
- Academic Search Index
- Journal :
- Oncogene
- Publication Type :
- Academic Journal
- Accession number :
- 11426692
- Full Text :
- https://doi.org/10.1038/sj.onc.1206735