Prostate stromal cells participate in the processes through which androgens regulate normal and cancerous prostate development. In their research, the investigators studied the responsiveness of human prostate stromal cell models to androgens and they developed a specific androgen-responsive human prostate stromal cell model (WPMY-AR cells) to profile for AR- and androgen-induced changes in gene expression using microarrays.
While immortalized human prostate stromal cell lines and primary prostate stromal cell cultures did not require androgens for in vitro growth, they grew slightly faster in the presence of synthetic androgen. AR expression in these cell lines was only 0.1%-3.4% of the level in LNCaP cells. This was validated by transfecting an androgen sensitive reporter construct in the cell lines with no significant increase in signal in response to exogenous androgens. However, co-transfection with an androgen reporter along with an AR expression vector resulted in increased response to androgens in the WPMY-AR cells. Infection of WPMY cells with wildtype AR resulted in comparable expression of AR to LNCaP cells. Stimulation of these cells with DHT resulted in increase androgen regulated gene expression, but no other morphologic changes from controls cells. Microarray demonstrated only 8 genes with differential expression by addition of DHT to the control cells, compared with 172 genes in the DHT stimulated WPMY1-AR cells. Pathways most prominently affected were in Cancer, Cytokine-Cytokine Receptor Interaction, TGF-β pathway, Wnt pathway, and Hedgehog Signaling pathway. AR overexpression alone without ligand could induce, but mainly repressed genes in WPMY-1 cells, but these effects were sometimes reversed in the presence of ligand. Regarding the paracrine effect of stromal cells on epithelial cells, the researchers stimulated WPMY-1 cells with androgen, collected the conditioned media and applied it to LNCaP cells in culture. The conditioned media stimulated LNCaP cells to grow more rapidly.
Tanner MJ, Welliver RC Jr, Chen M, Shtutman M, Godoy A, Smith G, Mian BM, Buttyan
PLoS One. 2011 Jan 18;6(1):e16027
Editor's Commentary - Effects of androgen receptor and androgen on gene expression in prostate stromal fibroblasts and paracrine signaling to prostate cancer cells