Characterizations of Factors Affecting Androgen Receptor Transcriptional Regulation in Prostate Cancer

摘要

Androgen Receptor Trapped clone-27 (ART-27) is a transcriptional coactivator of the androgen receptor (AR) that was identified in yeast two- hybrid screen using the AR as bait (see Markus et al). Recent studies suggest that the ART-27 protein is expressed in normal differentiated epithelial cells of the prostate and breast, in contrast to the stroma, where ART-27 is not expressed. Expression of ART-27 in LNCaP cells, an androgen-dependent prostate cancer cell line, reduces androgen-mediated cellular proliferation, suggesting that ART-27 plays a role in suppressing cell growth. Consistent with a growth suppressive function, ART-27 protein is not detected in human prostate cancers or in the undifferentiated developing fetal prostate gland, whereas at a later stage of fetal prostate development when differentiated epithelial cells are evident ART-27 is detected. These results suggest that the lack of ART-27 in prostate cancer may occur as a result of de-differentiation. We propose that ART-27, via its activity as an AR coactivator, controls AR responsive genes that suppress proliferation and promote differentiation. Strategies to restore ART-27 expression could effectively treat local or metastatic prostate cancers by reestablishing a differentiated state and inhibiting cellular proliferation.