Immunohistochemical localization of the retinoic Acid receptors in human prostate.
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.
Richter
Frank
F
Department of Surgery, Division of Urology and Laboratory Medicine and Pathology, UMDNJ-New Jersey Medical School, Newark 07103, USA.
Joyce
Alina
A
Fromowitz
Frank
F
Wang
Shulun
S
Watson
John
J
Watson
Richard
R
Irwin
Robert J
RJ
Huang
Hosea F S
HF
D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D011467:Prostate / Q000378:metabolism*; D011470:Prostatic Hyperplasia / Q000378:metabolism; D019048:Prostatic Intraepithelial Neoplasia / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000378:metabolism*; D000072482:Retinoic Acid Receptor alpha; D014018:Tissue Distribution; D000097768:Retinoic Acid Receptor gamma
D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D000097768:Retinoic Acid Receptor gamma; C000607071:RARA protein, human; C082925:retinoic acid receptor beta