The relationship of neuroendocrine carcinomas to anti-tumor therapies in TRAMP mice

Yao Tang, Linbo Wang, Olga Goloubeva, Mohammad Afnan Khan, Dong Ik Lee, Arif Hussain

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND. Neuroendocrine differentiation and neuroendocrine carcinoma (NEC) have been linked to androgen deprivation in prostate cancers. No previous study has directly connected neuroendocrine phenotypes to chemotherapy. The pathogenesis of prostatic NEC has not yet been determined. METHODS. Using the transgenic adenocarcinoma of mouse prostate (TRAMP) model, we studied tumor progression after hormone ablation (castration) and/or chemotherapy (docetaxel), and analyzed the incidence of NEC as a function of the anti-tumor therapies. Non-treated mice were used as controls. Protein expressions in tumor tissues were analyzed by Western blots and immunohistochemistry. RESULTS. Although all animals developed prostate cancer, no NEC was found in control mice. However, over 30% of the mice that received an anti-tumor therapy developed NEC. A similar incidence of NEC was found in the castration-only and docetaxel-only treatment groups, while a higher incidence was observed in the combined treatment (castration and docetaxel) group. The NEC-bearing mice had smaller tumors in their prostates and lived longer than mice with adenocarcinoma (ADC-only). However, NEC tumors had a higher proliferative index and greater potential for metastasis and drug-resistance, as evidenced by significantly higher expression levels of PCNA, S100A4, and Pgp, but lower levels of E-cadherin. SV40 T-antigen was highly expressed in both NEC and ADC tumors. CONCLUSIONS. Stress induced by anti-cancer treatments may play a role in NEC development. Although NEC and ADC differ in their expressions of many proteins, a high level of SV40 T-antigen in both tumor types suggest a common progenitor.

Original languageEnglish (US)
Pages (from-to)1763-1773
Number of pages11
JournalProstate
Volume69
Issue number16
DOIs
StatePublished - Dec 1 2009
Externally publishedYes

Keywords

  • Neuroendocrine carcinoma
  • Prostate cancer
  • Tramp mice

ASJC Scopus subject areas

  • Oncology
  • Urology

Fingerprint Dive into the research topics of 'The relationship of neuroendocrine carcinomas to anti-tumor therapies in TRAMP mice'. Together they form a unique fingerprint.

Cite this