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

Soo Ok Lee1, Wei Lou, Min Hou

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

Oncogene
|September 13, 2003
PubMed

Insights

Interleukin-4 (IL-4) activates the androgen receptor (AR) in prostate cancer cells, promoting prostate-specific antigen (PSA) expression even without androgens. This IL-4 signaling pathway, involving Akt, may drive androgen-independent prostate cancer progression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • Androgen receptor (AR) signaling is crucial for prostate cancer (PC) development and progression.
  • Abnormal AR activation by non-androgens contributes to androgen-independent PC.
  • Elevated interleukin-4 (IL-4) levels are observed in hormone-refractory prostate cancer patients.

Purpose of the Study:

  • To investigate the role of IL-4 in activating the AR in prostate cancer cells.
  • To explore IL-4's potential contribution to androgen-independent prostate cancer progression.
  • To elucidate the signaling pathways involved in IL-4-mediated AR activation.

Main Methods:

  • Investigated IL-4's effect on AR-mediated gene expression (PSA, ARE-luciferase) in LNCaP cells under androgen-depleted conditions.
  • Assessed IL-4's impact on AR nuclear translocation and ARE binding.
  • Utilized an Akt-specific inhibitor (LY294002) to block the Akt pathway.

Main Results:

  • IL-4 significantly enhanced AR-mediated prostate-specific antigen (PSA) expression and androgen-responsive element (ARE) activity in LNCaP cells.
  • IL-4 sensitized the AR, enabling activation by very low androgen levels (10 pM R1881).
  • IL-4 promoted AR nuclear translocation and increased AR binding to AREs, an effect abrogated by LY294002, indicating Akt pathway involvement.

Conclusions:

  • IL-4 activates the androgen receptor (AR) and enhances PSA expression in prostate cancer cells via the Akt signaling pathway.
  • IL-4-induced AR activation contributes to the molecular mechanisms underlying androgen-independent prostate cancer progression.
  • Targeting IL-4 signaling may offer a therapeutic strategy for hormone-refractory prostate cancer.

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