Retinoic acid receptors (RARs) are nuclear
transcription factors that mediate the effects of
retinoids. Aberrant expression and regulation of RARs have been linked to various
malignancies, including
steroid-related breast and
cervical cancers. Our previous results also suggest that
prostate cancer is associated with altered RAR signaling. To understand the relationship between RAR signaling and
prostate cancer, the current study examined the cellular distribution of RAR-alpha, -beta, and -gamma in human prostate tissues exhibiting different pathologic conditions. In histologically normal epithelium, both RAR-alpha and -gamma were present throughout the epithelium with minimal nuclear accumulation.
RAR-beta was present only in basal epithelial nuclei. On the contrary, RAR-alpha was significantly increased in the nuclei of
luminal epithelial cells, and both
RAR-beta and -gamma were increased in basal and
luminal epithelial nuclei in glands exhibiting
benign prostatic hyperplasia (BPH). RAR-alpha was also increased in
luminal epithelial nuclei in glands exhibiting prostatic intra-epithelial
neoplasia (PIN). In these glands,
RAR-beta was persisting in basal epithelial nuclei that were also
RAR-gamma positive. In low- and intermediate-grade cancerous glands, RAR-alpha was also significantly increased in
luminal epithelial nuclei, and a strong
RAR-gamma signal was seen in some cells.
RAR-beta was absent in these glands. Both RAR-alpha and -gamma were also increased in high-grade
cancer cells. In conclusion, current results demonstrated changes in cellular distribution of RAR-alpha and -gamma in human prostate tissues exhibiting different pathologies. These results suggest links between altered RAR signaling and deregulated cell growth and/or
tumorigenic transformation of prostate epithelial cells.