Interleukin-4 enhances prostate-specific antigen expression by activation of the androgen receptor and Akt pathway

Soo Ok Lee, Wei Lou, Min Hou, Sergio A. Onate, Allen C Gao

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

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 (10pM 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.

Original languageEnglish (US)
Pages (from-to)7981-7988
Number of pages8
JournalOncogene
Volume22
Issue number39
DOIs
StatePublished - Sep 11 2003
Externally publishedYes

Keywords

  • Androgen receptor
  • IL-4
  • Prostate cancer
  • PSA

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

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