Scherl Alexis, Li Jiu-Feng, Cardiff Robert D, Schreiber-Agus Nicole
Department of Molecular Genetics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York, USA.
Prostate. 2004 Jun 1;59(4):448-59. doi: 10.1002/pros.20020.
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.
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.
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.
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.
RAS 通路的激活与包括前列腺癌在内的多种人类癌症的发病机制有关。在此，我们采用转基因方法来评估 RAS 对前列腺癌发生的潜在作用。
构建了前列腺素-RAS（Pb-RAS）转基因小鼠，并证明其在前列腺叶中高水平表达活化的 RAS。通过组织学和使用相关标志物的免疫组织化学方法，将转基因前列腺与正常对照进行比较。
Pb-RAS 转基因前列腺呈现肿瘤性变化，包括低级别前列腺上皮内瘤变，以及向肠杯状细胞表型的化生变化。在这些转基因前列腺中发现高水平的杯状细胞特异性肽 Itf/Tff3，这与最近的微阵列研究结果一致，该研究表明 ITF/TFF3 在人类前列腺癌样本中上调。
Pb-RAS 小鼠模型可用于阐明前列腺癌发生的早期事件，以及研究肠化生的机制及其与前列腺癌的潜在相关性。
