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The relationship of neuroendocrine carcinomas to anti‐tumor therapies in TRAMP mice
Author(s) -
Tang Yao,
Wang Linbo,
Goloubeva Olga,
Khan Mohammad Afnan,
Lee DongIk,
Hussain Arif
Publication year - 2009
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.21026
Subject(s) - tramp , medicine , docetaxel , prostate cancer , neuroendocrine differentiation , adenocarcinoma , prostate , immunohistochemistry , metastasis , cancer , castration , cancer research , pathology , oncology , hormone
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. Prostate 69: 1763–1773, 2009. © 2009 Wiley‐Liss, Inc.