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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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Identification of key genes and specific pathways potentially involved in androgen-independent,

Sha Zhu1, Lili Jiang1,2, Liuyan Wang3

  • 1Department of Immunology, Collaborative Innovation Center of Cancer Chemoprevention, College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China, chzsha06@126.com.

Cancer Management and Research
|January 19, 2019
PubMed
Abstract

Insights

Mitoxantrone resistance in prostate cancer (PCa) is a major challenge. This study identified 636 differentially expressed genes in resistant tumors, revealing potential targets for improved therapy.

Area of Science:

  • Oncology
  • Genomics
  • Pharmacology

Background:

  • Androgen-refractory prostate cancer (PCa) treatment is limited by resistance to mitoxantrone (MTX).
  • Understanding the genetic basis of MTX resistance is crucial for developing effective therapies.

Purpose of the Study:

  • To identify genetic alterations associated with MTX resistance in androgen-independent PCa.
  • To explore potential therapeutic targets for overcoming MTX resistance.

Main Methods:

  • Established human PCa xenografts (VCaP, CWR22) in immunodeficient mice.
  • Administered MTX with or without castration until tumor relapse.
  • Utilized microarray technology to screen for differentially expressed genes (DEGs) and Ingenuity Pathway Analysis for data interpretation.

Main Results:

  • Identified 636 DEGs (fold change ≥1.5; P<0.05) in MTX-resistant castration-resistant PCa (CRPC) xenografts.
  • Validated 18 DEGs, showing high correlation with microarray data (Pearson's r=0.87).
  • Network analysis revealed deregulated genes involved in androgen synthesis, drug efflux, ATP synthesis, and vascularization.

Conclusions:

  • The study provides insights into the genetic mechanisms of MTX resistance in advanced PCa.
  • Identified key pathways and genes that represent potential targets for overcoming therapeutic resistance.
Keywords:
castration-resistant prostate cancerdifferentially expressed genesdrug resistancegene expression profiling

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