Origin of androgen-insensitive poorly differentiated tumors in the transgenic adenocarcinoma of mouse prostate model

Neoplasia. 2007 Nov;9(11):938-50. doi: 10.1593/neo.07562.


Following castration, the transgenic adenocarcinoma of mouse prostate (TRAMP) model demonstrates rapid development of SV40-Tag-driven poorly differentiated tumors that express neuroendocrine cell markers. The cell population dynamics within the prostates of castrated TRAMP mice were characterized by analyzing the incorporation of 5-bromodeoxyuridine (BrdUrd) and the expression of SV40-Tag, synaptophysin, and androgen receptor (AR). Fourteen days postcastration, the remaining epithelial cells and adenocarcinoma cells were nonproliferative and lacked detectable SV40-Tag or synaptophysin expression. In contrast, morphologically distinct intraglandular foci were identified which expressed SV40-Tag, synaptophysin, and Ki67, but that lacked AR expression. These proliferative SV40-Tag and synaptophysin-expressing intraglandular foci were associated with the rare BrdUrd-retaining cells. These foci expanded rapidly in the postcastration prostate environment, in contrast to the AR- and SV40-Tag-expressing adenocarcinoma cells that lost SV40-Tag expression and underwent apoptosis after castration. Intraglandular foci of synaptophysin-expressing cells were also observed in the prostates of intact TRAMP mice at a comparable frequency; however, they did not progress to rapidly expanding tumors until much later in the life of the mice. This suggests that the foci of neuroendocrine-like cells that express SV40-Tag and synaptophysin, but lack AR, arise independent of androgen-deprivation and represent the source of the poorly differentiated tumors that are the lethal phenotype in the TRAMP model.

Keywords: Prostate cancer; TRAMP; androgen-insensitive; neuroendocrine; synaptophysin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / pathology*
  • Androgens / physiology*
  • Animals
  • Antigens, Polyomavirus Transforming / analysis
  • Antigens, Polyomavirus Transforming / genetics
  • Apoptosis
  • Bromodeoxyuridine / metabolism
  • Cell Proliferation
  • Disease Models, Animal
  • Hepatocyte Nuclear Factor 3-beta / analysis
  • Lymphatic Metastasis
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Orchiectomy
  • Prostatic Neoplasms / blood supply
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology*
  • Receptors, Androgen / analysis
  • Simian virus 40 / immunology
  • Synaptophysin / analysis


  • Androgens
  • Antigens, Polyomavirus Transforming
  • Foxa2 protein, mouse
  • Receptors, Androgen
  • Synaptophysin
  • Hepatocyte Nuclear Factor 3-beta
  • Bromodeoxyuridine