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

Oncogene volume 22, pages 7981–7988 (2003)Cite this article

An Editorial Expression of Concern to this article was published on 01 October 2021

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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.

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Abbreviations

IL-4:

interleukin-4

AR:

androgen receptor

ARE:

androgen response element

PSA:

prostate specific-antigen

Stat:

signal transducers and activators of transcription

MAPK:

mitogen-activated protein kinase

PI3 K:

phosphatidylinositol (PI) 3-kinase

HF:

hydroxyflutamide

CS-FBS:

charcoal-stripped fetal bovine serum

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Acknowledgements

We thank Dr Chawnshang Chang, University of Rochester, for the gift of AR expression vector.

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Authors and Affiliations

  1. Department of Medicine and Pharmacology & Therapeutics, Roswell Park Cancer Institute, Buffalo, 14263, NY, USA

    Soo Ok Lee, Wei Lou, Min Hou & Allen C Gao

  2. Department of Cell Biology and Physiology, University of Pittsburgh Medical Center, Pittsburgh, 15213, PA, USA

    Sergio A Onate

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  1. Soo Ok Lee
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  2. Wei Lou
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  3. Min Hou
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  5. Allen C Gao
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Correspondence to Allen C Gao.

Additional information

This research was supported by grants from NIH CA90271 and US Army Medical Research Materiel Command AMRMC Prostate Cancer Research Program Grant DAMD17-01-1-0089

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Lee, S., Lou, W., Hou, M. et al. Interleukin-4 enhances prostate-specific antigen expression by activation of the androgen receptor and Akt pathway. Oncogene 22, 7981–7988 (2003). https://doi.org/10.1038/sj.onc.1206735

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