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Updated: Aug 15, 2026
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Molecular alterations in primary prostate cancer after androgen ablation therapy
Carolyn J M Best1, John W Gillespie, Yajun Yi
1Pathogenetics Unit, Laboratory of Pathology, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. bestcar@mail.nih.gov
Purpose:
After an initial response to androgen ablation, most prostate tumors recur, ultimately progressing to highly aggressive androgen-independent cancer. The molecular mechanisms underlying progression are not well known in part due to the rarity of androgen-independent samples from primary and metastatic sites.
Experimental Design:
We compared the gene expression profiles of 10 androgen-independent primary prostate tumor biopsies with 10 primary, untreated androgen-dependent tumors. Samples were laser capture microdissected, the RNA was amplified, and gene expression was assessed using Affymetrix Human Genome U133A GeneChip. Differential expression was examined with principal component analysis, hierarchical clustering, and Student's t testing. Analysis of gene ontology was done with Expression Analysis Systematic Explorer and gene expression data were integrated with genomic alterations with Differential Gene Locus Mapping.
Results:
Unsupervised principal component analysis showed that the androgen-dependent and androgen-independent tumors segregated from one another. After filtering the data, 239 differentially expressed genes were identified. Two main gene ontologies were found discordant between androgen-independent and androgen-dependent tumors: macromolecule biosynthesis was down-regulated and cell adhesion was up-regulated in androgen-independent tumors. Other differentially expressed genes were related to interleukin-6 signaling as well as angiogenesis, cell adhesion, apoptosis, oxidative stress, and hormone response. The Differential Gene Locus Mapping analysis identified nine regions of potential chromosomal deletion in the androgen-independent tumors, including 1p36, 3p21, 6p21, 8p21, 11p15, 11q12, 12q23, 16q12, and 16q21.
Conclusions:
Taken together, these data identify several unique characteristics of androgen-independent prostate cancer that may hold potential for the development of targeted therapeutic intervention.
Insights
Prostate cancer progression to androgen-independent tumors involves altered gene expression, with decreased macromolecule biosynthesis and increased cell adhesion. These findings offer new targets for treating aggressive prostate cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Prostate cancer often recurs after androgen ablation, progressing to aggressive androgen-independent disease.
- Understanding the molecular mechanisms of this progression is crucial but limited by sample rarity.
Purpose of the Study:
- To compare gene expression profiles of androgen-independent and androgen-dependent prostate tumors.
- To identify molecular differences driving prostate cancer progression.
Main Methods:
- Gene expression profiling of 10 androgen-independent and 10 androgen-dependent prostate tumors.
- Laser capture microdissection, RNA amplification, and Affymetrix GeneChip analysis.
- Principal component analysis, hierarchical clustering, and gene ontology analysis.
Main Results:
- Androgen-dependent and independent tumors segregated distinctly based on gene expression.
- 239 differentially expressed genes were identified.
- Macromolecule biosynthesis was down-regulated and cell adhesion up-regulated in androgen-independent tumors.
- Interleukin-6 signaling, angiogenesis, apoptosis, and hormone response genes were also altered.
- Nine chromosomal deletion regions were identified in androgen-independent tumors.
Conclusions:
- Androgen-independent prostate cancer exhibits unique molecular characteristics.
- These findings may lead to targeted therapeutic interventions for advanced prostate cancer.
