Journal Article

Prostatic intraepithelial neoplasia and adenocarcinoma in mice expressing a probasin-<i>Neu</i> oncogenic transgene

Zhe Li, Matthias Szabolcs, Joseph D. Terwilliger and Argiris Efstratiadis

in Carcinogenesis

Volume 27, issue 5, pages 1054-1067
Published in print May 2006 | ISSN: 0143-3334
Published online January 2006 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgi324
Prostatic intraepithelial neoplasia and adenocarcinoma in mice expressing a probasin-Neu oncogenic transgene

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NEU (ERBB2) and other members of the epidermal growth factor receptor (EGFR) family have been implicated in human prostate cancer (CAP) development and progression to an androgen-independent state, but the extent of involvement and precise role of this signaling pathway remain unclear. To begin addressing such open questions in an animal model, we have developed a transgenic line in which an oncogenic Neu cDNA (Neu*) driven by the probasin gene promoter is overexpressed in the mouse prostate and causes development of prostatic intraepithelial neoplasia (PIN) that progresses to invasive carcinoma. Expression profiling using microarrays, which was selectively validated and extended by immunophenotyping of Neu*-induced PIN and CAP, led to the identification of some novel biomarkers and also revealed increased expression of Egfr, Erbb3 and phosphorylated androgen receptor. In view of this information from our mouse model, which can be used to analyze further the role of Erbb signaling in prostatic tumorigenesis, we examined human prostate cancer tissue arrays by immunohistochemistry. Based on statistical analyses of the results, we propose the testable hypothesis that ERBB3, shown to be expressed in 86% of the human CAP cases that we examined, is the pivotal element of the Erbb pathway promoting tumorigenesis by heterodimerization with NEU or EGFR, while a NEU/EGFR dimer does not appear to play a significant role in CAP.

Keywords: AI, androgen-independent; Akt1, thymoma viral proto-oncogene 1; AR, androgen receptor; BPH, benign prostatic hyperplasia; BrdU, 5-bromo-2′-deoxy-uridine; CAP, prostate cancer; Neu*, activated Neu (Erbb2) receptor; IHC, immunohistochemistry; PAH, prostatic atypical hyperplasia; PIN, prostatic intraepithelial neoplasia; TANT, tumor-adjacent normal tissue

Journal Article.  9706 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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