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.