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Updated: May 30, 2026
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Development of a castrate resistant transplant tumor model of prostate cancer
Leigh Ellis1, Kristin Lehet, Swathi Ramakrishnan
1Roswell Park Cancer Institute, Genitourinary Program, Grace Cancer Drug Center, Buffalo, New York, USA.
Background:
Currently, limited mouse models that mimic the clinical course of castrate resistant prostate development currently exist. Such mouse models are urgently required to conduct pre-clinical studies to assist in the understanding of disease progression and the development of rational therapeutic strategies to treat castrate resistant prostate cancer.
Methods:
Wild type intact FVB male mice were injected by subcutaneous injection with Myc-CaP cells to establish androgen sensitive Myc-CaP tumors. Tumor bearing mice were castrated and resulting tumors serially passaged in pre-castrated FVB male mice to produce a bone fide Myc-CaP castrate resistant tumor.
Results:
Immunohistochemical analysis revealed that initial androgen sensitive Myc-CaP tumors had strong nuclear transcriptional active androgen receptor expression, as indicated by marked c-MYC staining and were highly proliferative. Castration of tumor bearing animals resulted in cytoplasmic relocation of androgen receptor concurrent with loss of transcriptional activity and tumor proliferation. Serial passaging of castrate refractory Myc-CaP in pre-castrated male FVB mice resulted in the development of a bona fide castrate resistant Myc-CaP tumor which pheno-copied the original androgen sensitive parental Myc-CaP tumor.
Conclusions:
Developing a murine castrate transplant resistant tumor model that mimics the clinical course of human castrate resistant prostate cancer will create better opportunities to understand the development of castrate resistant prostate cancer and also allow for more rapid pre-clinical studies to stratify rational novel therapies for this lethal form of prostate cancer.
Insights
Researchers developed a new mouse model for castrate-resistant prostate cancer. This model accurately mimics human disease progression, aiding in the development of new prostate cancer therapies.
Area of Science:
- Oncology
- Urology
- Cancer Biology
Background:
- Limited availability of mouse models accurately reflecting castrate-resistant prostate cancer (CRPC) hinders research.
- There is an urgent need for preclinical models to study CRPC progression and therapeutic strategies.
Purpose of the Study:
- To develop and characterize a novel murine model for castrate-resistant prostate cancer.
- To establish a reliable preclinical tool for investigating CRPC development and treatment.
Main Methods:
- Wild-type FVB male mice were inoculated with Myc-CaP cells to form androgen-sensitive tumors.
- Tumors were serially passaged in castrated mice to generate a castrate-resistant model.
Main Results:
- Androgen-sensitive tumors exhibited nuclear androgen receptor (AR) expression and high proliferation.
- Castration led to AR relocation and suppressed tumor growth.
- Serial passaging in castrated mice yielded a castrate-resistant Myc-CaP tumor that phenocopied the parental tumor.
Conclusions:
- A new murine model for castrate-resistant prostate cancer has been successfully developed.
- This model closely mimics human CRPC, offering a valuable platform for preclinical studies.
- The model facilitates a better understanding of CRPC development and the evaluation of novel therapies.
