title: Development of a castrate resistant transplant tumor model of prostate cancer.
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.
authors.affiliation: Roswell Park Cancer Institute, Genitourinary Program, Grace Cancer Drug Center, Buffalo, New York, USA.
authors.forename: Leigh
authors.initials: L
authors.lastname: Ellis
authors.forename: Kristin
authors.initials: K
authors.lastname: Lehet
authors.forename: Swathi
authors.initials: S
authors.lastname: Ramakrishnan
authors.forename: Remi
authors.initials: R
authors.lastname: Adelaiye
authors.forename: Roberto
authors.initials: R
authors.lastname: Pili
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D009368:Neoplasm Transplantation; D009919:Orchiectomy; D011467:Prostate / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism
chemical_list: D011944:Receptors, Androgen