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Updated: May 11, 2026

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
07:25

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

Published on: March 6, 2018

Hypoxic tumor kinase signaling mediated by STAT5A in development of castration-resistant prostate cancer

Kathrine Røe1, Åse Bratland, Ljiljana Vlatkovic

  • 1Department of Oncology, Akershus University Hospital, Lørenskog, Norway. Kathrine.Roe@ahus.no

Plos One
|May 16, 2013
PubMed

Insights

Androgen-deprivation therapy for prostate cancer may lead to castration-resistant disease by inducing hypoxia and increasing signal transducer and activator of transcription 5A (STAT5A) kinase activity. STAT5A is a potential biomarker and therapeutic target for advanced prostate cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Androgen-deprivation therapy (ADT) is initially effective for prostate cancer but can lead to castration-resistant (CR) disease.
  • Tumor hypoxia is correlated with poor prognosis in prostate cancer and may influence ADT resistance.
  • The tumor kinome undergoes changes during ADT, potentially promoting CR disease development.

Purpose of the Study:

  • To investigate how ADT affects the tumor kinome and promotes CR prostate cancer.
  • To determine the influence of tumor hypoxia on ADT-induced kinome changes.
  • To identify potential biomarkers and therapeutic targets for advanced prostate cancer.

Main Methods:

  • Utilized peptide substrate microarrays to analyze kinase activity in CWR22 prostate carcinoma xenografts across different disease stages (ADT-naïve, AD, ADL, CR).
  • Assessed the impact of hypoxia by comparing xenograft kinase profiles with those from hypoxic and normoxic prostate carcinoma cell cultures.
  • Evaluated clinical relevance by analyzing patient prostatectomy samples from locally advanced, ADT-naïve, or early CR disease stages.

Main Results:

  • Revealed high kinase activity mediated by signal transducer and activator of transcription 5A (STAT5A) in CR prostate cancer.
  • Detected elevated STAT5A kinase activity in regressing androgen-deprived (ADL) xenografts prior to the emergence of CR growth.
  • Observed increased STAT5A kinase activity upon exposure of prostate carcinoma cells to hypoxia.

Conclusions:

  • Long-term ADT may induce tumor hypoxia, stimulating STAT5A kinase activity and promoting renewed CR tumor growth.
  • STAT5A is identified as a potential biomarker for advanced prostate cancer.
  • STAT5A represents a potential therapeutic target protein for advanced prostate cancer.

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