Development of a castrate resistant transplant tumor model of prostate cancer

Leigh Ellis, Kristin Lehet, Swathi Ramakrishnan, Remi Adelaiye, Roberto Pili

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)587-591
Number of pages5
JournalProstate
Volume72
Issue number6
DOIs
StatePublished - May 1 2012
Externally publishedYes

Fingerprint

Prostatic Neoplasms
Transplants
Neoplasms
Androgens
Androgen Receptors
Castration
Subcutaneous Injections
Disease Progression
Prostate
Staining and Labeling
Bone and Bones
Therapeutics

Keywords

  • castrate resistant prostate cancer
  • mouse models
  • MYC
  • prostate cancer

ASJC Scopus subject areas

  • Urology
  • Oncology

Cite this

Development of a castrate resistant transplant tumor model of prostate cancer. / Ellis, Leigh; Lehet, Kristin; Ramakrishnan, Swathi; Adelaiye, Remi; Pili, Roberto.

In: Prostate, Vol. 72, No. 6, 01.05.2012, p. 587-591.

Research output: Contribution to journalArticle

Ellis, L, Lehet, K, Ramakrishnan, S, Adelaiye, R & Pili, R 2012, 'Development of a castrate resistant transplant tumor model of prostate cancer', Prostate, vol. 72, no. 6, pp. 587-591. https://doi.org/10.1002/pros.21465
Ellis, Leigh ; Lehet, Kristin ; Ramakrishnan, Swathi ; Adelaiye, Remi ; Pili, Roberto. / Development of a castrate resistant transplant tumor model of prostate cancer. In: Prostate. 2012 ; Vol. 72, No. 6. pp. 587-591.
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