Prostatic intraepithelial neoplasia and intestinal metaplasia in prostates of probasin-RAS transgenic mice.
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-RAS (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.
Scherl
Alexis
A
Department of Molecular Genetics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York, USA.
Li
Jiu-Feng
JF
Cardiff
Robert D
RD
Schreiber-Agus
Nicole
N
D000727:Androgen-Binding Protein; D000818:Animals; D002471:Cell Transformation, Neoplastic; D004064:Digestive System / Q000473:pathology; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008679:Metaplasia; D051379:Mice; D008822:Mice, Transgenic; D019048:Prostatic Intraepithelial Neoplasia / Q000235:genetics* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation; D018631:ras Proteins / Q000096:biosynthesis*
D000727:Androgen-Binding Protein; C027519:probasin; D018631:ras Proteins