Changes in mitotic reorientation and Wnt/AR signaling in rat prostate epithelial cells exposed to subchronic testosterone.

The aim of the present study was to investigate the changes in mitotic reorientation and relative differential gene expression in rat prostate epithelial cells following long-term exposure to testosterone propionate (TP). Sprague-Dawley rats were randomly divided into two groups as follows: TP group, which received 3.7 mg/kg/day TP for 30 days (n=10); and control group, in which rats were injected with olive oil (n=10). Microscopic analysis of the prostate tissue was performed by immunohistochemical analysis and hematoxylin and eosin staining. Differential gene expression analysis was performed via gene microarray, and a total of five genes (Dkk3, Ran, Fas, Tgm4 and Wnt2) were selected and their expression levels were verified using reverse transcription-polymerase chain reaction. For rats treated with TP, mitosis was significantly reoriented, becoming parallel to the basement membrane. By contrast, in the control group cells mitotic orientation remained perpendicular to the basement membrane. Genes such as Ran and Tgm4 in the androgen receptor (AR) signaling pathway and Wnt2 in the Wnt signaling pathway, were upregulated following treatment with TP. Conversely, the Dkk3 and Fas genes were downregulated following treatment with TP. In conclusion, mitotic orientation of prostate epithelial cells was altered following long-term administration of TP. Wnt and AR signaling pathways influenced cell proliferation and may have participated in the mitotic orientation change.