Genes differentially expressed in the peripheral zone compared to the transitional zone of the normal human prostate and their potential regulation by ETS factors

Abstract

Prostate cancer (PCa) is a clinically heterogeneous and multifocal disease with a clinical outcome that is difficult to predict. Notably, predisposition to develop prostate cancer is different among the prostate zones, with the peripheral zone (PZ) or prostate proper as the most frequent site compared to the transitional zone (TZ). Translocations between the TMPRSS2 gene and a number of members of the ETS family are frequently found in PCa. Here, we examined expression differences among the two zones by laser microdissection of normal tissues from PCa patients to separate glands from stroma, and investigated the gene expression differences in the glands of the PZ compared to those of the TZ using microarray analysis. We identified 9 genes involved in the so-called metastatic cascade, to be highly differentially expressed in the normal glands of the PZ compared to those of the TZ. The genes which were found to be up-regulated in the PZ compared to the TZ are commonly up-regulated in tumors. These findings may explain the lower susceptibility for PCa of the TZ compared to the PZ. According to bioinformatic analysis, 8/9 of these genes may be potentially regulated by ETS transcription factors.