title: The relationship of neuroendocrine carcinomas to anti-tumor therapies in TRAMP mice.
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..
authors.affiliation: Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: Yao
authors.initials: Y
authors.lastname: Tang
authors.forename: Linbo
authors.initials: L
authors.lastname: Wang
authors.forename: Olga
authors.initials: O
authors.lastname: Goloubeva
authors.forename: Mohammad Afnan
authors.initials: MA
authors.lastname: Khan
authors.forename: Dongik
authors.initials: D
authors.lastname: Lee
authors.forename: Arif
authors.initials: A
authors.lastname: Hussain
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000556:secondary; D000726:Androgen Antagonists / Q000008:administration & dosage / Q000009:adverse effects*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D018278:Carcinoma, Neuroendocrine / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology / Q000556:secondary; D049109:Cell Proliferation; D000077143:Docetaxel; D004359:Drug Therapy, Combination; D015994:Incidence; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009363:Neoplasm Proteins / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016019:Survival Analysis; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: C116614:ABCG2 protein, human; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000726:Androgen Antagonists; D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D043823:Taxoids; D000077143:Docetaxel