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Loss of Nkx3.1 expression in the transgenic adenocarcinoma of mouse prostate model
Author(s) -
Bethel Carlise R.,
Bieberich Charles J.
Publication year - 2007
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.20579
Subject(s) - tramp , prostate cancer , prostate , adenocarcinoma , immunohistochemistry , carcinogenesis , pathology , genetically modified mouse , biology , cancer research , medicine , transgene , cancer , gene , genetics
BACKGROUND The transgenic adenocarcinoma of mouse prostate (TRAMP) model has been extensively characterized at the histological and molecular levels, and has been shown to mimic significant features of human prostate cancer. However, the status of Nkx3.1 expression in the TRAMP model has not been elucidated. METHODS Immunohistochemical analyses were performed using dorsal, lateral, and ventral prostate (VP) lobes from ages 6 to 30 weeks. Quantitative RT‐PCR analyses were performed to determine relative mRNA expression. RESULTS Heterogeneous loss of Nkx3.1 was observed in hyperplastic lesions of the ventral, dorsal, and lateral lobes. At 6 weeks of age, the ventral lobe displayed profound loss of Nkx3.1. Diminished Nkx3.1 protein was observed in well‐ to moderately‐differentiated cancer lesions of all lobes. Poorly differentiated (PD) tumors stained negatively for Nkx3.1. Quantitative RT‐PCR analyses revealed the presence of Nkx3.1 mRNA in each lobe at all ages, albeit reduced to variable levels. CONCLUSIONS These data suggest that disease progression in the TRAMP model may be driven by loss of function of Nkx3.1, in addition to p53 and Rb. Lobe‐specific disease progression in the TRAMP model correlates with the reduction of Nkx3.1 protein. Regulation of Nkx3.1 expression during tumorigenesis appears to occur by post‐transcriptional and post‐translational mechanisms. Prostate 67: 1740–1750, 2007. © 2007 Wiley‐Liss, Inc.