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Prostatic intraepithelial neoplasia and intestinal metaplasia in prostates of probasin ‐ RAS transgenic mice
Author(s) -
Scherl Alexis,
Li JiuFeng,
Cardiff Robert D.,
SchreiberAgus Nicole
Publication year - 2004
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.20020
Subject(s) - intraepithelial neoplasia , intestinal metaplasia , high grade prostatic intraepithelial neoplasia , medicine , metaplasia , pathology , prostate , genetically modified mouse , transgene , biology , cancer , dysplasia , gene , biochemistry
BACKGROUND Activation of the RAS pathway has been implicated in the pathogenesis of many types of human cancers, including prostate cancer. Here we employed a transgenic approach to assess the potential contribution of RAS to prostate carcinogenesis. METHODS Probasin‐RA S ( Pb‐RAS ) transgenic mice were generated and shown to express high levels of activated RAS in the prostate lobes. Transgenic prostates were compared to normal controls by histology and immunohistochemistry with relevant markers. RESULTS Pb ‐ RAS transgenic prostates exhibit neoplastic changes including low‐grade prostatic intraepithelial neoplasia, and metaplastic changes towards an intestinal goblet cell phenotype. The finding of high levels of the goblet cell‐specific peptide Itf/Tff3 in these transgenic prostates is in accordance with recent microarray studies showing that ITF / TFF3 is upregulated in human prostate cancer samples. CONCLUSIONS The Pb ‐ RAS mouse model could be useful for elucidating the early events in prostate carcinogenesis, as well as for studying the mechanisms and potential prostate cancer relevance of intestinal metaplasia. © 2004 Wiley‐Liss, Inc.