Dissociation of epithelial and neuroendocrine carcinoma lineages in the transgenic adenocarcinoma of mouse prostate model of prostate cancer

Teresa Chiaverotti, Suzana S. Couto, Annemarie Donjacour, Jian Hua Mao, Hiroki Nagase, Robert Cardiff, Gerald R. Cunha, Allan Balmain

Research output: Contribution to journalArticle

139 Citations (Scopus)

Abstract

The transgenic adenocarcinoma of mouse prostate (TRAMP) model is widely used in prostate cancer research because of rapid tumor onset and progression. The transgenic mouse is on a C57BL/6 (B6) background and expresses SV40 T-antigen under the probasin promoter. The strong genetic component of susceptibility to prostate cancer in humans prompted us to investigate the effect of mouse strain background (FVB and B6) on incidence, progression, and pathology of prostate cancer in this model. Because TRAMP lesions are unique but differ from conventional prostatic intraepithelial neoplasia because the epithelium and stroma are affected diffusely, we designated them as "atypical hyperplasia of Tag." Although the incidence and severity of atypical hyperplasia of Tag is similar, FVB-TRAMP mice live significantly shorter lives than B6-TRAMP mice because of the rapid development and progression of neuroendocrine carcinomas. This is associated with an increased frequency of neuroendocrine precursor lesions in young TRAMP mice, detectable at 4 weeks after birth. These lesions show properties of bipotential stem cells and co-express markers of epithelial (E-cadherin) and neuroendocrine (synaptophysin) lineages, as well as the transcription factors Foxa1 and Foxa2. Transplantation studies using TRAMP prostatic ducts suggested that neuroendocrine carcinomas arise independently from atypical hyperplasias or other epithelial lesions. Adenocarcinomas were not seen in our cohort. Thus, neuroendocrine carcinomas are the principal malignancy in this model and may develop from bipotential progenitor cells at an early stage of prostate tumorigenesis.

Original languageEnglish (US)
Pages (from-to)236-246
Number of pages11
JournalAmerican Journal of Pathology
Volume172
Issue number1
DOIs
StatePublished - Jan 1 2008

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Neuroendocrine Carcinoma
Transgenic Mice
Prostate
Prostatic Neoplasms
Adenocarcinoma
Hyperplasia
Cadherins
Stem Cells
Prostatic Intraepithelial Neoplasia
Polyomavirus Transforming Antigens
Synaptophysin
Incidence
Genetic Predisposition to Disease
Neoplasms
Carcinogenesis
Transcription Factors
Epithelium
Transplantation
Parturition
Pathology

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Dissociation of epithelial and neuroendocrine carcinoma lineages in the transgenic adenocarcinoma of mouse prostate model of prostate cancer. / Chiaverotti, Teresa; Couto, Suzana S.; Donjacour, Annemarie; Mao, Jian Hua; Nagase, Hiroki; Cardiff, Robert; Cunha, Gerald R.; Balmain, Allan.

In: American Journal of Pathology, Vol. 172, No. 1, 01.01.2008, p. 236-246.

Research output: Contribution to journalArticle

Chiaverotti, Teresa ; Couto, Suzana S. ; Donjacour, Annemarie ; Mao, Jian Hua ; Nagase, Hiroki ; Cardiff, Robert ; Cunha, Gerald R. ; Balmain, Allan. / Dissociation of epithelial and neuroendocrine carcinoma lineages in the transgenic adenocarcinoma of mouse prostate model of prostate cancer. In: American Journal of Pathology. 2008 ; Vol. 172, No. 1. pp. 236-246.
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