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. Copyright 2004 Wiley-Liss, Inc.
BACKGROUND: Activation of the RAS pathway has been implicated in the pathogenesis of many types of humancancers, 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 humanprostate 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. Copyright 2004 Wiley-Liss, Inc.
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