Gene Expression Studies Of Prostate Hyperplasia In Prolactin Transgenic Mice

Benign prostatic hyperplasia (BPH) and prostate cancer are age-related diseases, affecting a majority of elderly men in the western world, and are known to be influenced by several different hormones, including sex hormones. Although the hormone prolactin (PRL) is well known to exert trophic effects on prostate cells, its involvement in pathophysiological conditions is still poorly characterized. In order to evaluate the potential role of PRL in promoting prostate growth, we have used a recently developed transgenic mouse model that overexpresses the PRL gene specifically in the prostate (Pb-PRL transgenic mice). The PRL transgenic mice develop a significant prostate hyperplasia which increases with age. The prostates of the Pb-PRL transgenic mice display a prominent stromal hyperplasia with mild epithelial dysplastic features, leading to an increased stromal/epithelial ratio. Accumulation of secretory material is also a major characteristic. By using cDNA microarray analysis we have obtained interesting insights into the molecular mechanisms involved in the prostate hyperplasia. Of particular interest is the significance of reduced apoptosis for the development/progression of the prostate phenotype. This finding was further confirmed by immunohistochemical analysis using two different apoptosis markers. Moreover, in line with the prominent expansion of the stromal compartment were the identified changes in gene expression seen in the PRL transgenic prostate, suggesting that activation of the stroma is important for the development of the prostate hyperplasia.Overall, we demonstrate histological and Molecular similarities between the prostate hyperplasia of Pb-PRL transgenic mice and human prostate pathology, including both BPH and prostate cancer.