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Updated: Feb 10, 2026

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
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A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer

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AIRE promotes androgen-independent prostate cancer by directly regulating IL-6 and modulating tumor microenvironment

Rashi Kalra1, Ella Bhagyaraj1, Drishti Tiwari1

  • 1Department of Molecular Biology, Council of Scientific and Industrial Research, Institute of Microbial Technology, Sector 39A, Chandigarh, 160036, India.

Oncogenesis
|May 26, 2018
PubMed

Insights

The autoimmune regulator (AIRE) protein promotes prostate cancer progression by increasing tumor aggressiveness and resistance to therapy. Reduced AIRE levels in mice significantly inhibited tumor growth, suggesting AIRE as a therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Immunology

Background:

  • Prostate cancer progression involves a shift from androgen dependence to independence.
  • The molecular mechanisms driving this transition and enabling therapeutic resistance remain incompletely understood.
  • Understanding these factors is crucial for developing effective prostate cancer treatments.

Purpose of the Study:

  • To investigate the role of the autoimmune regulator (AIRE) in prostate cancer progression.
  • To elucidate the mechanisms by which AIRE influences tumor microenvironment and aggressiveness.
  • To evaluate the therapeutic potential of targeting AIRE in prostate cancer.

Main Methods:

  • Comparative analysis of AIRE expression in androgen-dependent and -independent prostate cancer cells.
  • Investigation of AIRE regulation by transcription factor Elk-1.
  • Assessment of AIRE's impact on IL-6 expression and cancer cell survival/invasiveness.
  • Analysis of AIRE's effect on tumor-associated macrophage polarization.
  • Xenograft mouse model studies comparing AIRE-sufficient and AIRE-deficient mice.

Main Results:

  • AIRE exhibits differential expression, being significantly higher in androgen-independent prostate cancer cells.
  • AIRE upregulates Interleukin-6 (IL-6) and enhances cancer cell resistance to drug-induced death and invasiveness.
  • AIRE promotes M2 polarization of tumor-associated macrophages via cytokine modulation.
  • AIRE-deficient mice showed significantly reduced tumor growth and lymphadenopathy compared to AIRE-sufficient mice.

Conclusions:

  • AIRE is a key factor in promoting prostate cancer progression and therapeutic resistance.
  • AIRE influences the tumor microenvironment, enhancing malignancy and immune evasion.
  • Targeting AIRE presents a potential therapeutic strategy for advanced prostate cancer.

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