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- Title
Interleukin-4 enhances prostate-specific antigen expression by activation of the androgen receptor and Akt pathway.
- Authors
Soo Ok Lee, Jean-Noël; Wei Lou; Min Hou, Jean-Noël; Onate, Sergio A.; Gao, Allen C.
- 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
- Subjects
ANDROGENS; TRANS men; PROSTATE cancer; GENES; INTERLEUKIN-4; CANCER cells
- Publication
Oncogene, 2003, Vol 22, Issue 39, p6037
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/sj.onc.1206735