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Updated: Apr 14, 2026

An Orthotopic Murine Model of Human Prostate Cancer Metastasis
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An Orthotopic Murine Model of Human Prostate Cancer Metastasis

Published on: September 18, 2013

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ERG deregulation induces IGF-1R expression in prostate cancer cells and affects sensitivity to anti-IGF-1R agents

Caterina Mancarella1, Irene Casanova-Salas2, Ana Calatrava3

  • 1CRS Development of Biomolecular Therapies, Experimental Oncology Lab, Rizzoli Orthopaedic Institute, Bologna, Italy.

Oncotarget
|April 25, 2015
PubMed

Insights

Identifying prostate cancer patients for targeted therapy is crucial. The TMPRSS2-ERG (T2E) fusion gene correlates with higher insulin-like growth factor receptor (IGF-1R) expression, guiding the use of IGF-1R inhibitors.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Targeted therapy selection remains a clinical challenge in prostate cancer (PCa).
  • Understanding the molecular interplay between TMPRSS2-ERG (T2E) fusion and insulin-like growth factor receptor (IGF-1R) can optimize treatment strategies.

Purpose of the Study:

  • To investigate the molecular relationship between the T2E fusion gene and IGF-1R expression in PCa.
  • To evaluate the efficacy of IGF-1R inhibitors, alone and in combination with abiraterone acetate, in T2E-positive PCa.

Main Methods:

  • Analysis of IGF-1R expression in PCa cell lines and radical prostatectomy specimens.
  • Chromatin immunoprecipitation (ChIP) to assess ERG binding to the IGF-1R promoter.
  • In vitro sensitivity assays for IGF-1R inhibitors and abiraterone acetate.

Main Results:

  • T2E gene expression positively correlated with both mRNA and protein levels of IGF-1R.
  • ERG directly modulated IGF-1R protein levels, and ERG binds to the IGF-1R promoter.
  • IGF-1R inhibition was more effective in T2E-positive cells, with synergistic effects observed when combined with abiraterone acetate.

Conclusions:

  • The T2E fusion gene can serve as a biomarker for selecting PCa patients for IGF-1R inhibitor therapy.
  • Combination therapy of anti-IGF-1R antibodies and anti-androgen agents is recommended for T2E-expressing PCa patients.
Keywords:
ETS fusion genesanti-IGF-1R agentsinsulin-like growth factor receptor 1prostate cancer

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